Benzopyran derivative and antiallergic agent

专利摘要:
The present invention provides a compound having high toxicity in terms of toxicity, having a stronger antiallergic action, and in particular, an action of inhibiting immediate and delayed allergic reactions. Benzopyran derivatives represented by general formula (I) or their physiologically acceptable salts are excellent as active ingredients of anti-allergic groups: (Wherein R 1 represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms, and any one of R 2 , R 3 , R 4 and R 5 is an alkoxyl group or carboxy group substituted with a hydroxyl group); Substituted alkoxyl groups, others represent hydrogen atoms).
公开号:KR20030015827A
申请号:KR1020020036133
申请日:2002-06-26
公开日:2003-02-25
发明作者:다카가키히데쓰구；다나베신고；기무라노부유키；아오키야스오
申请人:다이니혼 잉키 가가쿠 고교 가부시키가이샤；
IPC主号:

专利说明:

Benzopyran derivatives and anti-allergic agents {BENZOPYRAN DERIVATIVE AND ANTIALLERGIC AGENT}
[2] The present invention relates to a benzopyran derivative useful as an antiallergic agent and an antiallergic agent comprising the benzopyran derivative or its physiologically acceptable salt as an active ingredient.
[3] International Publication No. WO 92/13852 (US Pat. No. 54,28059) discloses that benzopyran derivatives represented by the general formula (III) and their physiologically acceptable salts are useful for use as anti-allergic agents, and also have very low toxicity. It is disclosed that it is a high safety compound:
[4]
[5] (Wherein R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms, one of R ² , R ³ , R ⁴ and R ⁵ represents an alkoxyl group, and the other is a hydrogen atom) ).
[6] In addition, Japanese Patent Laid-Open No. 7-145189 (US Pat. No. 55,255,953) discloses a glycosyl group at position 3 of benzopyran, and Japanese Laid-Open Patent Publication No. 7-145190 (US Pat. No. 55,255,953) discloses the use of benzopyran. A benzopyran derivative and a physiologically acceptable salt thereof, each having a glycosyl group at position 4 and a glycosyl group at position 7 of benzopyran in Japanese Patent Application Laid-Open No. 8-198890 (spec. US Pat. No. 55,80552). It is disclosed that this compound is useful as an antiallergic agent and is also a very low toxicity and high safety compound.
[7] There has been a need for compounds having a stronger antiallergic action, particularly immediate and delayed allergic reactions, while maintaining safety in the toxicity of these benzopyran derivatives.
[8] As benzopyran derivatives other than the above, Japanese Patent Application Laid-Open No. 9-315967 (US Pat. No. 5,598,595) discloses that a benzopyran derivative represented by formula (VI) is useful as a therapeutic agent for heart disease.
[9]
[10] (Wherein R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms, and R ⁴ represents an alkoxyl group having 1 to 4 carbon atoms substituted with a hydroxyl group). However, it is not known that the compounds described in this publication have excellent antiallergic action.
[11] Donald T. Witiak, Journal of Medical Chemistry, Vol. 31, 1437p-1445p, 1988 (Donald.T.Witiak, J.Med.Chem., Vo1.31, P.1437-1445, 1988) and the United States. Patent 4845121 discloses that benzopyran derivatives represented by formula (V) are useful as antithrombotic agents:
[12]
[13] (In formula, R <^3> and R <^4> represents a hydrogen atom, a halogen atom, a hydroxyl group, the alkyl group of 1-6 carbon atoms, except that R <^3> and R <^4> together are a hydrogen atom.). However, it is not known at all that the compounds described in these documents are effective for the treatment of both immediate and delayed allergies and are very useful as agents having few side effects.
[14] The problem to be solved by the present invention is to provide a compound having high toxicity in terms of toxicity, stronger anti-allergic action, and in particular, an action of inhibiting immediate and delayed allergic reactions.
[1] 1 is a delayed asthma reaction in an asthma-induced medium administration group (after the induction of asthma reaction, no test drug administration), a positive control prednisolone administration group and the compound 216 administration group. The graph shows the relationship between the increase rate of airway resistance and the time and the area under the curve (AUC _4-8 ) from 4 to 8 hours after induction of asthma.
[15] That is, the present invention provides an antiallergic agent comprising, as an active ingredient, a benzopyran derivative represented by formula (I) or a physiologically acceptable salt thereof to solve the above problems:
[16]
[17] (Wherein R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms, and any one of R ² , R ³ , R ⁴ and R ⁵ is an alkoxyl group or carboxy group substituted with a hydroxyl group); Substituted alkoxyl groups, others represent hydrogen atoms).
[18] Moreover, this invention provides the benzopyran derivative represented by general formula (II) in order to solve the said subject:
[19]
[20] (Wherein R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms, any one of R ² , R ³ , R ⁴ and R ⁵ represents an alkoxyl group substituted with a carboxy group, Others represent hydrogen atoms).
[21] Hereinafter, the present invention will be described in detail.
[22] In the benzopyran derivatives represented by the general formula (I) and the benzopyran derivatives represented by the general formula (II) of the present invention, the alkyl group having 1 to 10 carbon atoms of R ¹ may be a linear alkyl group. A gaseous alkyl group may be sufficient. Examples of such alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, s-butyl, t-butyl and n-. Pentyl group, n-hexyl group, 2-methylpentyl group, n-heptyl group, 1-ethylpentyl group, 4-methylpentyl group, 1-ethylbutyl group, n-octyl group, 1-ethylhexyl group, n- Decyl group, n-dodecyl group, and the like.
[23] Similarly, an alkenyl group having 2 to 10 carbon atoms of R ¹ may be a straight alkenyl group or a branched alkenyl group, and as such an alkenyl group, for example, a vinyl group or a pro Phenyl group, pentenyl group, hexenyl group, heptenyl group, octenyl group, nonyl group, decenyl group, 3-methyl-2-butenyl group, geranyl group and the like. Among these alkenyl groups, alkenyl groups having 4 to 8 carbon atoms are particularly preferable.
[24] In the benzopyran derivative represented by the general formula (I) and the benzopyran derivative represented by the general formula (II) of the present invention, any one of R ² , R ³ , R ⁴ and R ⁵ is represented and substituted with a hydroxyl group. As the alkoxyl group which was used, for example, 2-hydroxyethoxy group, 3-hydroxypropyloxy group, 4-hydroxybutoxy group, 2,3-dihydroxypropyloxy group, 3,4-dihydroxy An oxybutoxy group etc. are mentioned. Among these, an alkoxyl group having 1 to 4 carbon atoms is preferable, and an alkoxyl group substituted with one or two hydroxyl groups is particularly preferable.
[25] Similarly, as an alkoxyl group which any one of R <^2> , R <^3> , R <^4> and R <^5> represents and substituted by the carboxy group, For example, 1-hydroxycarbonylmethoxy group, 2-hydroxycarbonylethoxy group, 3-hydroxycarbonylpropyloxy group, 4-hydroxycarbonyl butoxy group, etc. are mentioned. Among these, an alkoxyl group having 1 to 4 carbon atoms excluding a portion of the carboxyl group is preferable, and an alkoxyl group substituted with one carboxyl group is particularly preferable.
[26] The outline of the manufacturing method of the benzopyran derivative represented by the said General formula (I) used by this invention, or the benzopyran derivative represented by the said General formula (II) of this invention is demonstrated.
[27] The benzopyran derivatives represented by the general formulas (I) and (II) can be prepared, for example, according to the following reaction pathways:
[28]
[29] In the reaction route, first, the hydroxyl group of dihydroxyacetophenone (a) is protected by the benzyl group to obtain compound (b). Next, after condensation reaction of compound (b) and dimethyl carbonate is performed to obtain a keto ester body (c), the compound (d) is obtained by reacting with benzoyl peroxide. Here, the benzyl group which is a protecting group of a hydroxyl group is deprotected by hydrocracking, and is treated with an acid, and it is set as benzoyloxy body (f).
[30] Furthermore, the hydroxyl group on the aromatic ring of this benzoyloxy body (f) is protected by the benzyl group, and it is set as compound (g), and a methoxymethyl group is introduce | transduced into position 4, and compound (h) is obtained. After debenzoylation of compound (h), the hydroxyl group at position 3 is alkylated to obtain compound (j). Alkylation of a hydroxyl group can be made into a conventional alkylation reaction by reaction with alkyl halide, sulfate ester, allyl sulfonic acid ester, or the like. Subsequently, the protecting group of the hydroxyl group on an aromatic ring is deprotected and compound (k) is obtained.
[31] When obtaining the benzopyran derivative represented by the said general formula (I) whose R <^2> is the alkoxyl group substituted by the hydroxyl group, the hydroxyl group on the aromatic ring of compound (k) or compound (m) is a hydroxyl group in which some hydrogen atoms were protected. What is necessary is just to alkoxylate with the alkylating agent substituted with the following, and to carry out deprotection reaction of the protected hydroxyl group continuously.
[32] Moreover, in order to demonstrate the manufacturing method of the benzopyran derivative represented by the said general formula (I) and general formula (II) in detail, the manufacturing method of the benzopyran derivative in which the hydroxyl group on the benzene ring was alkoxylated by 2-hydroxyethyl group It demonstrates below.
[33] First, an alkoxylation reaction is carried out in which brominated-2-acetoxyethyl is reacted with compound (k) in an organic solvent in the presence of a basic substance.
[34] As a basic substance used here, inorganic salts, such as sodium hydrogencarbonate, sodium carbonate, potassium hydrogencarbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, t-butoxy sodium, t Basic substances, such as metal alcohols, such as -butoxy potassium, metal hydrides, such as sodium hydride and potassium hydride, are mentioned.
[35] Examples of the organic solvent used herein include hydrocarbon solvents such as benzene, toluene and xylene, ether solvents such as diethyl ether, tetrahydrofuran and 1,2-dimethoxyethane, and N, N-dimethylform. Amide solvents such as amide, N, N-dimethylacetamide and 1-methyl-2-pyrrolidinone.
[36] 0-100 degreeC is preferable and, as for the reaction temperature in the said reaction, 20-50 degreeC is especially preferable. In addition, the reaction time in the said reaction is 1 to 5 hours normally.
[37] Next, although acetyl group which is a protecting group is deprotected as needed, this reaction should just perform the deacetylation reaction under normal basic conditions. In this way, the benzopyran derivative in which the hydroxyl group on the aromatic ring was alkylated by the target 2-hydroxyethyl group can be manufactured.
[38] In addition, when obtaining the benzopyran derivative represented by the said general formula (I) which has the alkoxyl group substituted by two hydroxyl groups, an isopropylidene group can be used as two hydroxyl groups as a protecting group. Also in the case of using an alkylating agent protected with an isopropylidene group, the alkylation reaction of the benzopyran derivative hydroxyl group can be carried out in the same manner as described above, and the deprotection reaction after the alkylation reaction of the hydroxyl group is a conventional deprotection method of the isopropylidene group. The benzopyran derivatives having an alkoxyl group having two hydroxyl groups of interest can be produced by reacting at room temperature or by heating in acetic acid aqueous solution or hydrochloric acid-dioxy acid, for example.
[39] When R <^2> obtains the benzopyran derivative represented by said general formula (I) and general formula (II) which is an alkoxyl group substituted by the carboxy group, the hydroxyl group on the aromatic ring of compound (k) or compound (m), Some hydrogen atoms may be alkoxylated with an alkylating agent substituted with a protected carboxyl group, followed by a deprotection reaction. As an example, the manufacturing method of the benzopyran derivative which alkoxylated the hydroxyl group on the benzene ring by the hydroxycarbonylmethyl group is demonstrated below.
[40] First, alkoxylation is carried out by reacting the hydroxyl group of compound (k) or compound (m) with ethyl bromoacetate in an organic solvent in the presence of a basic substance.
[41] As a basic substance used for the said reaction, For example, inorganic salts, such as sodium hydrogencarbonate, sodium carbonate, potassium hydrogencarbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, t-butoxy Basic substances, such as metal alcohols, such as sodium and t-butoxy potassium, and metal hydrides, such as sodium hydride and potassium hydride, are mentioned.
[42] As the organic solvent used in the reaction, for example, hydrocarbon solvents such as benzene, toluene, xylene, ethyl solvents such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, N, N Amide solvents such as -dimethylformamide, N, N-dimethylacetamide, and 1-methyl-2-pyrrolidinone.
[43] 0-100 degreeC is preferable and, as for the reaction temperature of the said reaction, 20-50 degreeC is especially preferable. In addition, the reaction time of the said reaction is 1 to 5 hours normally.
[44] Next, although deprotection of the carboxy group which has a protecting group is carried out as needed, this reaction should just perform the deprotection reaction under normal basic conditions. In this way, the benzopyran derivative in which the hydroxyl group on the benzene ring of the target benzopyran derivative was alkoxylated by the hydroxycarbonylmethyl group can be manufactured.
[45] In the benzopyran derivatives represented by the general formulas (I) and (II), when R ¹ is an alkenyl group, in the above method, instead of alkoxylating the hydroxyl group at position 3, What is necessary is just to carry out alkenyloxylation of a hydroxyl group using a halogenated alkenyl, allyl sulfonic acid ester, etc. by a method by presence of a basic substance.
[46] The following compounds are mentioned as a specific example of the benzopyran derivative represented by the said General formula (I) used by this invention, and the benzopyran derivative represented by the said General formula (II) of this invention.
[47] 3-methoxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (1)), 3-ethoxy-4-hydroxy-5- (2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (2)), 3-propyloxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1 -Benzopyran-2-one (Compound (3)), 3-isopropyloxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (4) )), 3-butoxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (5)), 3- (s-butoxy)- 4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (6)), 3-pentyloxy-4-hydroxy-5- (2-hydroxy Ethoxy) -2H-1-benzopyran-2-one (Compound (7)), 3-hexyloxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran- 2-one (Compound (8)), 3- (2-methylpentyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (9) )), 3-heptyloxy-4-hydroxy-5- (2-hydroxyethoxy C) -2H-1-benzopyran-2-one (compound (10)),
[48] 3- (1-ethylpentyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (11)), 3- (4-ethylpentyl Oxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (12)), 3- (1-ethylbutoxy) -4-hydroxy -5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (13)), 3-octyloxy-4-hydroxy-5- (2-hydroxyethoxy)- 2H-1-benzopyran-2-one (Compound (14)), 3- (1-ethylhexyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran 2-one (compound (15)),
[49] 3-decyloxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (16)), 3-vinyloxy-4-hydroxy-5 -(2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (17)), 3- (1-propenyloxy) -4-hydroxy-5- (2-hydroxye Methoxy) -2H-1-benzopyran-2-one (compound (18)), 3- (1-butenyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1- Benzopyran-2-one (Compound (19)), 3- (1-hexenyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one ( Compound (20)),
[50] 3- (1-octenyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (21)), 3- (1-decenyl Oxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (22)), 3- (3-methyl-2-butenyloxy)- 4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (23)), 3-geranyloxy-4-hydroxy-5- (2-hydroxy Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (24)), 3-prenyloxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran 2-one (compound (25)),
[51] 3-methoxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (26)), 3-ethoxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (27)), 3-butoxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1 -Benzopyran-2-one (compound (28)), 3-hexyloxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (29) )), 3- (2-methylpentyloxy) -4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (30)),
[52] 3-octyloxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (31)), 3-decyloxy-4-hydroxy-5 -(3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (32)), 3- (1-propenyloxy) -4-hydroxy-5- (3-hydroxypropyl Oxy) -2H-1-benzopyran-2-one (compound (33)), 3- (1-octenyloxy) -4-hydroxy-5- (3-hydroxypropyloxy) -2H-1- Benzopyran-2-one (Compound (34)), 3-geranyloxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (35) ), 3-ethoxy-4-hydroxy-5- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (36)), 3-butoxy-4-hydroxy- 5- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (37)), 3- (s-butoxy) -4-hydroxy-5- (4-hydroxy moiety Methoxy) -2H-1-benzopyran-2-one (Compound (38)), 3-hexyloxy-4-hydroxy-5- (4-hydroxybutoxy) -2H-1-benzopyran-2 -On (compound (39)),
[53] 3- (1-ethylpentyloxy) -4-hydroxy-5- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (40)), 3-octyloxy-4- Hydroxy-5- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (41)), 3- (1-butenyloxy) -4-hydroxy-5- (4 -Hydroxybutoxy) -2H-1-benzopyran-2-one (compound (42)), 3-prenyloxy-4-hydroxy-5- (4-hydroxybutoxy) -2H-1- Benzopyran-2-one (Compound (43)), 3-ethoxy-4-hydroxy-5- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound ( 44)), 3-butoxy-4-hydroxy-5- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (45)),
[54] 3-hexyloxy-4-hydroxy-5- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (46)), 3-octyloxy-4-hydroxy Hydroxy-5- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (47)), 3-decyloxy-4-hydroxy-5- (2,3 -Dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (48)), 3- (1-hexenyloxy) -4-hydroxy-5- (2,3-dihydroxy Propyloxy) -2H-1-benzopyran-2-one (Compound (49)), 3- (3-methyl-2-butenyloxy) -4-hydroxy-5- (2,3-dihydroxy Propyloxy) -2H-1-benzopyran-2-one (compound (50)),
[55] 3-methoxy-4-hydroxy-5- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (51)), 3-ethoxy-4-hydroxy -5- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (52)), 3-hexyloxy-4-hydroxy-5- (3,4- Dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (53)), 3-octyloxy-4-hydroxy-5- (3,4-dihydroxybutoxy) -2H- 1-benzopyran-2-one (compound (54)), 3- (1-propenyloxy) -4-hydroxy-5- (3,4-dihydroxybutoxy) -2H-1-benzopyran 2-one (compound (55)),
[56] 3- (1-octenyloxy) -4-hydroxy-5- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (56)), 3-geranyl Oxy-4-hydroxy-5- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (Compound (57)), 3-methoxy-4-hydroxy-5- Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (58)), 3-ethoxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2- On (Compound (59)), 3-propyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (60)), 3-isopropyloxy-4 -Hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (61)),
[57] 3-butoxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (62)), 3- (s-butoxy) -4-hydroxy-5 -Hydroxycarbonylmethoxy-benzopyran-2-one (Compound (63)), 3-pentyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (64)), 3-hexyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (65)), 3- (2-methylpentyloxy) 4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (66)), 3-heptyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H -1-benzopyran-2-one (compound (67)),
[58] 3- (1-ethylpentyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (68)), 3- (4-methylpentyloxy)- 4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (69)), 3- (1-ethylbutoxy) -4-hydroxy-5-hydroxycarbon Neylmethoxy-2H-1-benzopyran-2-one (Compound (70)), 3-octyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (71)), 3- (1-ethylhexyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (72)),
[59] 3-decyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (73)), 3-vinyloxy-4-hydroxy-5-hydroxy Carbonylmethoxy-2H-1-benzopyran-2-one (Compound (74)), 3- (1-propenyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran 2-one (compound (75)), 3- (1-butenyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (76)) 3- (1-hexenyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (77)),
[60] 3- (1-octenyloxy) -4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (78)), 3- (1-decenyloxy)- 4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (79)), 3- (3-methyl-2-butenyloxy) -4-hydroxy-5 -Hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (80)), 3-geranyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran- 2-one (Compound (81)), 3-prenyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (82)), 3-methoxy 4-Hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (83)), 3-ethoxy-4-hydroxy-5- (2 -Hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (84)), 3-butoxy-4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H -1-benzopyran-2-one (compound (85)), 3-hexyloxy-4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopy 2-one (compound (86)), 3-octyloxy-4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (87)) ,
[61] 3- (1-propenyloxy) -4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (88)), 3- (1- Octenyloxy) -4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (89)), 3-geranyloxy-4-hydroxy -5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (90)), 3-ethoxy-4-hydroxy-5- (3-hydroxycarbonyl Propyloxy) -2H-1-benzopyran-2-one (Compound (91)), 3-butoxy-4-hydroxy-5- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran 2-one (compound (92)), 3-hexyloxy-4-hydroxy-5- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (93) ),
[62] 3-octyloxy-4-hydroxy-5- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (94)), 3- (1-butenyloxy)- 4-hydroxy-5- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (95)), 3-prenyloxy-4-hydroxy-5- (3 -Hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (96)), 3-ethoxy-4-hydroxy-5- (4-hydroxycarbonylbutoxy) -2H- 1-benzopyran-2-one (compound (97)), 3-butoxy-4-hydroxy-5- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound ( 98)),
[63] 3-hexyloxy-4-hydroxy-5- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (99)), 3-octyloxy-4-hydroxy- 5- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (100)), 3- (1-octenyloxy) -4-hydroxy-5- (4-hydroxy Oxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (101)), 3-methoxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran 2-one (compound (102)), 3-ethoxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (103)),
[64] 3-propyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (104)), 3-isopropyloxy-4-hydroxy-6 -(2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (105)), 3-butoxy-4-hydroxy-6- (2-hydroxyethoxy) -2H- 1-benzopyran-2-one (Compound (106)), 3- (s-butoxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (107)), 3-pentyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (108)),
[65] 3-hexyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (109)), 3- (2-methylpentyloxy) -4 -Hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (110)), 3-heptyloxy-4-hydroxy-6- (2-hydroxy Methoxy) -2H-1-benzopyran-2-one (compound (111)), 3- (1-ethylpentyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1- Benzopyran-2-one (Compound (112)), 3- (4-methylpentyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one ( Compound (113)),
[66] 3- (1-ethylbutoxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (114)), 3-octyloxy-4- Hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (115)), 3- (1-ethylhexyloxy) -4-hydroxy-6- ( 2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (116)), 3-decyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1 -Benzopyran-2-one (Compound (117)), 3-vinyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (118) ),
[67] 3- (1-propenyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (119)), 3- (1-butenyl Oxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (120)), 3- (1-hexenyloxy) -4-hydroxy -6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (121)), 3- (1-octenyloxy) -4-hydroxy-6- (2-hydroxy Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (122)), 3- (1-decenyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H- 1-benzopyran-2-one (compound (123)),
[68] 3- (3-methyl-2-butenyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (124)), 3-gera Nyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (125)), 3-prenyloxy-4-hydroxy-6- ( 2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (126)), 3-methoxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1- Benzopyran-2-one (Compound (127)), 3-ethoxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (128)) ,
[69] 3- (butoxy) -4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (129)), 3-hexyloxy-4-hydroxy -6- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (130)), 3- (2-methylpentyloxy) -4-hydroxy-6- (3-hydroxy Oxypropyloxy) -2H-1-benzopyran-2-one (Compound (131)), 3-octyloxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran- 2-one (Compound (132)), 3-decyloxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (133)),
[70] 3- (1-propenyloxy) -4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound 134), 3- (1-octenyl Oxy) -4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (135)), 3-geranyloxy-4-hydroxy-6- ( 3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (136)), 3-ethoxy-4-hydroxy-6- (4-hydroxybutoxy) -2H-1- Benzopyran-2-one (Compound (137)), 3-butoxy-4-hydroxy-6- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (138)) ,
[71] 3- (s-butoxy) -4-hydroxy-6- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (139)), 3-hexyloxy-4- Hydroxy-6- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (140)), 3- (1-ethylpentyloxy) -4-hydroxy-6- (4 -Hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (141)), 3-octyloxy-4-hydroxy-6- (4-hydroxybutoxy) -2H-1-benzo Pyran-2-one (compound (142)), 3- (1-butenyloxy) -4-hydroxy-6- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (143)),
[72] 3-prenyloxy-4-hydroxy-6- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (144)), 3-ethoxy-4-hydroxy-6 -(2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (145)), 3-butoxy-4-hydroxy-6- (2,3-dihydroxy Propyloxy) -2H-1-benzopyran-2-one (Compound (146)), 3-hexyloxy-4-hydroxy-6- (2,3-dihydroxypropyloxy) -2H-1- Benzopyran-2-one (Compound (147)), 3-octyloxy-4-hydroxy-6- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound ( 148)), 3-decyloxy-4-hydroxy-6- (2, 3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (149)), 3- (1 -Hexenyloxy) -4-hydroxy-6- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (150)), 3- (3-methyl-2 -Butenyloxy) -4-hydroxy-6- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (151)), 3-methoxy-4-hydroxy Roxy-6- (3,4-dihydroxybutock ) -2H-1-benzopyran-2-one (Compound (152)), 3-ethoxy-4-hydroxy-6- (3,4-dihydroxybutoxy) -2H-1-benzopyran- 2-one (compound (153)),
[73] 3-hexyloxy-4-hydroxy-6- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (154)), 3-octyloxy-4-hydroxy Hydroxy-6- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (155)), 3- (1-propenyloxy) -4-hydroxy-6- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (156)), 3- (1-octenyloxy) -4-hydroxy-6- (3,4 -Dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (157)), 3-geranyloxy-4-hydroxy-6- (3,4-dihydroxybutoxy)- 2H-1-benzopyran-2-one (Compound (158)),
[74] 3-methoxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (159)), 3-ethoxy-4-hydroxy-6-hydroxycarbon Neylmethoxy-2H-1-benzopyran-2-one (Compound (160)), 3-propyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (161)), 3-isopropyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (162)), 3-butoxy-4-hydroxy -6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (163)), 3- (s-butoxy) -4-hydroxy-6-hydroxycarbonylmethoxy-benzopyran 2-one (compound (164)), 3-pentyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (165)),
[75] 3-hexyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (166)), 3- (2-methylpentyloxy) -4-hydroxy -6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (167)), 3-heptyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran 2-one (compound (168)), 3- (1-ethylpentyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (169)) , 3- (4-ethylpentyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (170)),
[76] 3- (1-ethylbutoxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (171)), 3-octyloxy-4-hydroxy- 6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (172)), 3- (1-ethylhexyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H -1-benzopyran-2-one (compound (173)), 3-decyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (174)) ), 3-vinyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (175)),
[77] 3- (1-propenyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (176)), 3- (1-butenyloxy)- 4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (177)), 3- (1-hexenyloxy) -4-hydroxy-6-hydroxycarbon Neylmethoxy-2H-1-benzopyran-2-one (Compound (178)), 3- (1-octenyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran- 2-one (compound (179)), 3- (1-decenyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (180)),
[78] 3- (3-Methyl-2-butenyloxy) -4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (181)), 3-geranyloxy- 4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (182)), 3-prenyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H -1-benzopyran-2-one (compound (183)), 3-methoxy-4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one ( Compound (184)), 3-ethoxy-4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (185)),
[79] 3-butoxy-4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (186)), 3-hexyloxy-4-hydroxy -6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (187)), 3-octyloxy-4-hydroxy-6- (2-hydroxycarbonyl Ethoxy) -2H-1-benzopyran-2-one (compound (188)), 3- (1-propenyloxy) -4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H -1-benzopyran-2-one (compound (189)), 3- (1-octenyloxy) -4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran 2-one (compound (190)),
[80] 3-geranyloxy-4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (191)), 3-ethoxy-4-hydroxy -6- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (192)), 3-butoxy-4-hydroxy-6- (3-hydroxycarbonyl Propyloxy) -2H-1-benzopyran-2-one (Compound (193)), 3-hexyloxy-4-hydroxy-6- (3-hydroxycarbonylpropyloxy) -2H-1-benzo Pyran-2-one (compound (194)), 3-octyloxy-4-hydroxy-6- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (195) ),
[81] 3- (1-butenyloxy) -4-hydroxy-6- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (196)), 3-prenyloxy -4-hydroxy-6- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (197)), 3-ethoxy-4-hydroxy-6- (4 -Hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (198)), 3-butoxy-4-hydroxy-6- (4-hydroxycarbonylbutoxy) -2H-1 -Benzopyran-2-one (compound (199)), 3-hexyloxy-4-hydroxy-6- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound ( 200)),
[82] 3-octyloxy-4-hydroxy-6- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound 201), 3- (1-octenyloxy) -4 -Hydroxy-6- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (202)), 3-methoxy-4-hydroxy-7- (2-hydroxy Ethoxy) -2H-1-benzopyran-2-one (Compound (203)), 3-ethoxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2 -One (compound 204), 3-propyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (205)), 3-iso Propyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (206)),
[83] 3-butoxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (207)), 3- (s-butoxy) -4-hydroxy Hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (208)), 3-pentyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (209)), 3-hexyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (210)), 3- (2-methylpentyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (211)),
[84] 3-heptyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (212)), 3- (1-ethylpentyloxy) -4- Hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (213)), 3- (4-ethylpentyloxy) -4-hydroxy-7- (2 -Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (214)), 3- (1-ethylbutoxy) -4-hydroxy-7- (2-hydroxyethoxy)- 2H-1-benzopyran-2-one (Compound (215)), 3-octyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (216)),
[85] 3- (1-ethylhexyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (217)), 3-decyloxy- 4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (218)), 3-vinyloxy-4-hydroxy-7- (2-hydroxy Ethoxy) -2H-1-benzopyran-2-one (Compound (219)), 3- (1-propenyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1 -Benzopyran-2-one (Compound (220)), 3- (1-butenyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (221)),
[86] 3- (1-hexenyloxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (222)), 3- (1-octenyl Oxy) -4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (223)), 3- (1-decenyloxy) -4-hydroxy -7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (224)), 3- (3-methyl-2-butenyloxy) -4-hydroxy-7- (2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (225)), 3-geranyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H- 1-benzopyran-2-one (compound (226)),
[87] 3-prenyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (227)), 3-methoxy-4-hydroxy-7 -(3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (228)), 3-ethoxy-4-hydroxy-7- (3-hydroxypropyloxy) -2H- 1-benzopyran-2-one (Compound (229)), 3- (s-butoxy) -4-hydroxy-7- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (230)), 3-hexyloxy-4-hydroxy-7- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (231)),
[88] 3- (2-methylpentyloxy) -4-hydroxy-7- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (232)), 3-octyloxy-4- Hydroxy-7- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (233)), 3-decyloxy-4-hydroxy-7- (3-hydroxypropyl Oxy) -2H-1-benzopyran-2-one (compound (234)), 3- (1-propenyloxy) -4-hydroxy-7- (3-hydroxypropyloxy) -2H-1- Benzopyran-2-one (Compound (235)), 3- (1-octenyloxy) -4-hydroxy-7- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one ( Compound (236)),
[89] 3-geranyloxy-4-hydroxy-7- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (237)), 3-ethoxy-4-hydroxy-7 -(4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (238)), 3-butoxy-4-hydroxy-7- (4-hydroxybutoxy) -2H- 1-benzopyran-2-one (compound (239)), 3- (s-butoxy) -4-hydroxy-7- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (240)), 3-hexyloxy-4-hydroxy-7- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (241)), 3- (1 -Ethylpentyloxy) -4-hydroxy-7- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (242)),
[90] 3-octyloxy-4-hydroxy-7- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (243)), 3- (1-butenyloxy) -4- Hydroxy-7- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (244)), 3-prenyloxy-4-hydroxy-7- (4-hydroxy moiety Methoxy) -2H-1-benzopyran-2-one (Compound (245)), 3-ethoxy-4-hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzopyran 2-one (compound (246)),
[91] 3-butoxy-4-hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (247)), 3-hexyloxy-4-hydroxy Hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (248)), 3-octyloxy-4-hydroxy-7- (2,3- Dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (249)), 3-decyloxy-4-hydroxy-7- (2,3-dihydroxypropyloxy) -2H -1-benzopyran-2-one (compound (250)), 3- (1-hexenyloxy) -4-hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzo Pyran-2-one (compound (251)),
[92] 3- (3-methyl-2-butenyloxy) -4-hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (252)), 3-methoxy-4-hydroxy-7- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (253)), 3-ethoxy-4-hydroxy -7- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (254)), 3-hexyloxy-4-hydroxy-7- (3,4- Dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (255)), 3-octyloxy-4-hydroxy-7- (3,4-dihydroxybutoxy) -2H- 1-benzopyran-2-one (compound (256)),
[93] 3- (1-propenyloxy) -4-hydroxy-7- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (257)), 3- (1 -Octenyloxy) -4-hydroxy-7- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (258)), 3-geranyloxy-4- Hydroxy-7- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (259)),
[94] 3-methoxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (260)), 3-ethoxy-4-hydroxy-7-hydroxycarbon Neylmethoxy-2H-1-benzopyran-2-one (Compound (261)), 3-propyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (262)), 3-isopropyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (263)), 3-butoxy-4-hydroxy -7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (264)), 3- (s-butoxy) -4-hydroxy-7-hydroxycarbonylmethoxy-benzopyran 2-one (compound (265)), 3-pentyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (266)), 3-hexyloxy Cy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (267)), 3- (2-methylpentyloxy) -4-hydroxy-7-hydroxy Oxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (268)),
[95] 3-heptyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (269)), 3- (1-ethylpentyloxy) -4-hydroxy- 7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (270)), 3- (4-ethylpentyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H- 1-benzopyran-2-one (compound (271)), 3- (1-ethylbutoxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (272)), 3-octyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (273)),
[96] 3- (1-ethylhexyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (274)), 3-decyloxy-4-hydroxy Hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (275)), 3-vinyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzo Pyran-2-one (compound (276)), 3- (1-propenyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (277)) ),
[97] 3- (1-butenyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (278)),
[98] 3- (1-hexenyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (279)), 3- (1-octenyloxy)- 4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (280)), 3- (1-decenyloxy) -4-hydroxy-7-hydroxycarbon Neylmethoxy-2H-1-benzopyran-2-one (Compound (281)), 3- (3-methyl-2-butenyloxy) -4-hydroxy-7-hydroxycarbonylmethoxy-2H-1 -Benzopyran-2-one (compound (282)), 3-geranyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (283)),
[99] 3-prenyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (284)), 3-methoxy-4-hydroxy-7- (2 -Hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (285)), 3-ethoxy-4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H -1-benzopyran-2-one (compound (286)), 3-butoxy-4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one ( Compound (287)), 3-hexyloxy-4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (288)),
[100] 3-octyloxy-4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (289)), 3- (1-propenyloxy)- 4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (290)), 3- (1-octenyloxy) -4-hydroxy- 7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (291)), 3-geranyloxy-4-hydroxy-7- (2-hydroxycarbonyl Ethoxy) -2H-1-benzopyran-2-one (Compound (292)), 3-ethoxy-4-hydroxy-7- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran 2-one (compound (293)),
[101] 3-butoxy-4-hydroxy-7- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (294)), 3-hexyloxy-4-hydroxy -7- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (295)), 3-octyloxy-4-hydroxy-7- (3-hydroxycarbonyl Propyloxy) -2H-1-benzopyran-2-one (Compound (296)), 3- (1-butenyloxy) -4-hydroxy-7- (3-hydroxycarbonylpropyloxy) -2H -1-benzopyran-2-one (compound (297)), 3-prenyloxy-4-hydroxy-7- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound (298)),
[102] 3-ethoxy-4-hydroxy-7- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (299)), 3-butoxy-4-hydroxy-7 -(4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (300)), 3-hexyloxy-4-hydroxy-7- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (301)), 3-octyloxy-4-hydroxy-7- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (302)), 3- (1-octenyloxy) -4-hydroxy-7- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (303)) ,
[103] 3-methoxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound 304), 3-ethoxy-4-hydroxy-8- (2-Hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (305)), 3-propyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1 -Benzopyran-2-one (Compound 306), 3-isopropyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (307) )), 3-butoxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (308)), 3- (s-butoxy)- 4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (309)), 3-pentyloxy-4-hydroxy-8- (2-hydroxy Ethoxy) -2H-1-benzopyran-2-one (Compound (310)), 3-hexyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran- 2-one (compound 311), 3- (2-methylpentyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound 312) )), 3-heptyloxy-4-hydroxy-8- (2- Idroxyethoxy) -2H-1-benzopyran-2-one (Compound (313)), 3- (1-ethylpentyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H -1-benzopyran-2-one (compound (314)),
[104] 3- (4-ethylpentyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound 315), 3- (1-ethyl part Methoxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (316)), 3-octyloxy-4-hydroxy-8- (2 -Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (317)), 3- (1-ethylhexyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (318)), 3-decyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (319)), 3-Vinyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (320)), 3- (1- Propenyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound 321), 3- (1-butenyloxy) -4- Hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound 322), 3- (1-hexenyloxy) -4-hydroxy-8- (2 -Hydroxyethoxy) -2H-1-benzopyran-2-one (compound (323)), 3- (1 -Octenyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound 324), 3- (1-decenyloxy) -4 -Hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (325)), 3- (3-methyl-2-butenyloxy) -4-hydroxy -8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (compound (326)), 3-geranyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (327)), 3-prenyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (328)), 3-methoxy-4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (329)),
[105] 3-ethoxy-4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (330)), 3-butoxy-4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (331)), 3-hexyloxy-4-hydroxy-8- (2-hydroxypropyloxy) -2H- 1-benzopyran-2-one (Compound (332)), 3- (2-methylpentyloxy) -4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2- One (compound (333)), 3-octyloxy-4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (334)), 3-decyloxy Cy-4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (335)), 3- (1-propenyloxy) -4-hydroxy- 8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (compound (336)), 3- (1-octenyloxy) -4-hydroxy-8- (3-hydroxy Propyloxy) -2H-1-benzopyran-2-one (Compound (337)), 3-geranyloxy-4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran- 2-one (compound (338)),
[106] 3-ethoxy-4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (339)), 3-butoxy-4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (340)), 3- (s-butoxy) -4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (341)), 3-hexyloxy-4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (342)), 3- (1-ethylpentyloxy) -4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound (343)), 3-octyloxy-4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound 344), 3- (1-butenyloxy) -4- Hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (compound 345), 3-prenyloxy-4-hydroxy-8- (4-hydroxy moiety Methoxy) -2H-1-benzopyran-2-one (Compound 346), 3-ethoxy-4-hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran 2-one (Compound (347)), 3-butoxy-4-hydroxy-8 -(2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (348)), 3-hexyloxy-4-hydroxy-8- (2,3-dihydro Oxypropyloxy) -2H-1-benzopyran-2-one (compound (349)),
[107] 3-octyloxy-4-hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (350)), 3-decyloxy-4-hydroxy Hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (351)), 3- (1-hexenyloxy) -4-hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (352)), 3- (3-methyl-2-butenyloxy) -4-hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (compound (353)), 3-methoxy-4-hydroxy-8- (3,4-dihydroxy moiety Methoxy) -2H-1-benzopyran-2-one (compound (354)),
[108] 3-ethoxy-4-hydroxy-8- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (355)), 3-hexyloxy-4-hydroxy Hydroxy-8- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (356)), 3-octyloxy-4-hydroxy-8- (3,4- Dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (357)), 3- (1-propenyloxy) -4-hydroxy-8- (3,4-dihydroxy moiety Methoxy) -2H-1-benzopyran-2-one (compound (358)), 3- (1-octenyloxy) -4-hydroxy-8- (3,4-dihydroxybutoxy) -2H -1-benzopyran-2-one (compound (359)),
[109] 3-geranyloxy-4-hydroxy-8- (3,4-dihydroxybutoxy) -2H-1-benzopyran-2-one (compound (360)), 3-methoxy-4-hydroxy Hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (361)), 3-ethoxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzo Pyran-2-one (compound (362)), 3-propyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (363)), 3-iso Propyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (364)), 3-butoxy-4-hydroxy-8-hydroxycarbonylmethoxy -2H-1-benzopyran-2-one (compound (365)), 3- (s-butoxy) -4-hydroxy-8-hydroxycarbonylmethoxy-benzopyran-2-one (compound (366) )),
[110] 3-pentyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (367)), 3-hexyloxy-4-hydroxy-8-hydroxy Carbonylmethoxy-2H-1-benzopyran-2-one (Compound (368)), 3- (2-methylpentyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran 2-one (compound (369)), 3-heptyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (370)), 3- (1 -Ethylpentyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (371)), 3- (4-ethylpentyloxy) -4-hydroxy -8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (372)), 3- (1-ethylbutoxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H -1-benzopyran-2-one (compound (373)), 3-octyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (374)) , 3- (1-ethylhexyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1 -Benzopyran-2-one (compound (375)), 3-decyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (376)),
[111] 3-vinyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (377)), 3- (1-propenyloxy) -4-hydroxy- 8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (378)), 3- (1-butenyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H- 1-benzopyran-2-one (compound (379)), 3- (1-hexenyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (380)), 3- (1-octenyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (381)),
[112] 3- (1-decenyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (382)), 3- (3-methyl-2-part Tenyloxy) -4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (compound (383)), 3-geranyloxy-4-hydroxy-8-hydroxycarbo Neylmethoxy-2H-1-benzopyran-2-one (Compound (384)), 3-prenyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one ( Compound (385)), 3-methoxy-4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (386)),
[113] 3-ethoxy-4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (387)), 3-butoxy-4-hydroxy- 8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (388)), 3-hexyloxy-4-hydroxy-8- (2-hydroxycarbonyl Ethoxy) -2H-1-benzopyran-2-one (Compound (389)), 3-octyloxy-4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran 2-one (Compound 390), 3- (1-propenyloxy) -4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one ( Compound (391)),
[114] 3- (1-octenyloxy) -4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (392)), 3-geranyloxy 4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (compound (393)), 3-ethoxy-4-hydroxy-8- (3 -Hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (394)), 3-butoxy-4-hydroxy-8- (3-hydroxycarbonylpropyloxy) -2H -1-benzopyran-2-one (compound (395)), 3-hexyloxy-4-hydroxy-8- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound (396)),
[115] 3-octyloxy-4-hydroxy-8- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (397)), 3- (1-butenyloxy)- 4-hydroxy-8- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (398)), 3-prenyloxy-4-hydroxy-8- (3 -Hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (compound (399)), 3-ethoxy-4-hydroxy-8- (4-hydroxycarbonylbutoxy) -2H- 1-benzopyran-2-one (compound (400)), 3-butoxy-4-hydroxy-8- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound ( 401)),
[116] 3-hexyloxy-4-hydroxy-8- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (compound (402)), 3-octyloxy-4-hydroxy- 8- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (403)), 3- (1-octenyloxy) -4-hydroxy-8- (4-hydroxy Roxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (404))
[117] The physiologically acceptable salts referred to in the present invention are, for example, alkali addition salts of the above compounds, and examples thereof include non-toxic salts such as sodium salts, potassium salts, magnesium salts, calcium salts, and ammonium salts. The physiologically acceptable salt of the benzopyran derivative represented by the said general formula (II) can be manufactured by a well-known method from the benzopyran derivative represented by the said general formula (II) obtained by the said method.
[118] The benzopyran derivatives represented by the general formula (II) and physiologically acceptable salts thereof used in the present invention have a low toxicity, as shown in the examples below, and have an action of inhibiting immediate and delayed allergic reactions. As an antiallergic agent, it is very useful for the treatment or prevention of various allergic diseases.
[119] An allergic disease referred to in the present invention is an allergic disease caused by excessive activation of the immune apparatus of a living body by an exogenous or endogenous antigen. For example, immediate asthma, delayed asthma, bronchial asthma, childhood asthma, lung鼻 閉), atopic dermatitis, allergic dermatitis, gallitis, rash, eczema, allergic conjunctivitis, allergic rhinitis, hay fever, food allergy, allergic gastroenteritis, allergic colitis, drug allergy, contact dermatitis , Autoimmune diseases and the like.
[120] The anti-allergic agent containing the benzopyran derivative represented by the general formula (II) and its physiologically acceptable salt as an active ingredient is oral or parenteral administration (for example, intravenous administration, subcutaneous administration, transdermal administration). Administration or rectal administration), and the administration can be carried out in the form of a formulation suitable for each administration method. These preparations are tablets, capsules, granules, fine granules, powders, troches, sublingual tablets, and suppositories depending on the purpose of use. I), ointment, ointment, emulsion, suspending agent, syrup, chewable, etc.
[121] In these preparations, for example, nontoxic excipients, binders, disintegrating agents, lubricants, and preservatives commonly used in this type of drug. ), Antioxidants, tonicity agents, buffers, coating agents, copulating agents, dissolution aids, bases, and dispersants It can be formulated by a conventional method using additives such as a separator, a stabilizer, a coloring agent, etc. Specific examples of these non-toxic additives are listed below.
[122] Firstly, excipients include, for example, starch and its derivatives (dextrin, carboxymethyl starch, etc.), cellulose and its derivatives (methyl cellulose, hydroxypropylmethylcellulose, etc.), sugars (lactose, white light, glucose). Etc.), silicic acid and silicates (natural aluminum silicate, magnesium silicate), carbonates (calcium carbonate, magnesium carbonate, sodium hydrogen carbonate, etc.), aluminum hydroxide magnesium, synthetic hydrotalcite, polyoxyethylene derivatives, monostearic acid Glycerin, sorbitan monoolefin, and the like.
[123] As the binder, for example, starch and its derivatives (alpha starch, dextrin, etc.), cellulose and its derivatives (ethylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, etc.), gum arabic, tragant, gelatin, Sugars (glucose, white sugar, etc.), ethanol, polyvinyl alcohol and the like.
[124] Examples of disintegrating agents include starch and its derivatives (carboxymethyl starch, hydroxypropyl starch and the like), cellulose and its derivatives (carboxymethyl cellulose, crystalline cellulose, hydroxypropylmethylcellulose and the like), carbonates (carbonates) Calcium, calcium hydrogen carbonate, etc.), tragant, gelatin, agar and the like.
[125] As the lubricant, for example, stearic acid, calcium stearate, magnesium stearate, talc, silicic acid and salts thereof (hard silicic anhydride, natural aluminum silicate), titanium oxide, calcium hydrogen phosphate, dry aluminum hydroxide gel, macro Macrogol and the like.
[126] As the preservative, for example, paraoxybenzoic acid esters, sulfites (sodium sulfite, sodium pyrosulfite, etc.), phosphates (sodium phosphate, calcium polyphosphate, sodium polyphosphate, sodium metaphosphate, etc.), alcohols (chloro Butanol, benzyl alcohol, etc.), benzalkonium chloride, benzethonium chloride, phenol, cresol, chlorocresol, dihydroacetic acid, dihydrosodium acetate, glycerin sorbate, saccharides and the like.
[127] Examples of the antioxidants include sulfites (sodium sulfite, sodium bisulfite, etc.), rongalit, erythorbic acid, L-ascorbic acid, cysteine, thioglycerol, and butylhydroxyanisol. , Dibutyl hydroxytoluene, propyl gallate, ascorbic acid palmitate, dl-α-tocopherol and the like.
[128] As a tonicity agent, sodium chloride, sodium nitrate, potassium nitrate, dextrin, glycerin, glucose, etc. are mentioned, for example. Examples of the buffer include sodium carbonate, hydrochloric acid, boric acid, and phosphates (sodium hydrogen phosphate).
[129] Examples of the coating agent include cellulose derivatives (hydroxypropyl cellulose, cellulose acetate, hydroxypropyl methyl cellulose phthalate, and the like), shellac, polyvinylpyrrolidone, and polyvinylpyridines (poly-2-vinyl). Pyridine, poly-2-vinyl-5-ethylpyridine, and the like), polyvinylacetyldiethylaminoacetate, polyvinyl alcohol phthalate, methacrylate-methacrylic acid copolymer, and the like.
[130] Examples of the mating agent include sugars (glucose, white sugar, lactose, and the like), sodium saccharin, sugar alcohols, and the like. As the dissolution aid, for example, ethylenediamine, nicotinic acid amide, sodium saccharin, citric acid, citrate, sodium benzoate, soaps, polyvinylpyrrolidone, polysorbates, sorbitan fatty acid esters, glycerin, Polypren glycol, benzyl alcohol, etc. are mentioned.
[131] As the base, for example, fatty acids (pork oil), vegetable oils (olive oil, sesame oil, etc.), animal oil, lanolin acid, petrolatum, paraffin, raw, resin, bentonite, glycerin, glycol oil, higher alcohols (stearyl Alcohol, cetanol, etc.) etc. are mentioned.
[132] Examples of the dispersant include gum arabic, tragant, cellulose derivatives (such as methyl cellulose), stearic acid polyesters, sorbitan sesquioleic acid, aluminum monostearate, sodium alginate, polysorbates, sorbitan fatty acid esters, and the like. Can be mentioned. Moreover, as a stabilizer, sulfites (sodium bisulfite, etc.), nitrogen, a carbon dioxide, etc. are mentioned, for example.
[133] Moreover, although content of the benzopyran derivative represented by general formula (II) in such a formulation changes with the formulation, it is preferable that it is generally 0.01-100 weight%.
[134] The dosage of the anti-allergic agent of the present invention can vary widely depending on the type of warm-blooded animals, including humans, the severity of symptoms, and the judgment of a doctor. 0.01-50 mg is preferable per day, and 0.05-10 mg is especially preferable. In addition, the dosage in the case of parenteral administration is preferably in the range of preferably 0.01 to 10 mg, particularly preferably 0.01 to 5 mg per 1 kg of body weight per day. The dose can be administered once or several times a day, and can be appropriately changed depending on the severity of the patient's symptoms and the doctor's diagnosis.
[135] Example
[136] Next, although an Example demonstrates this invention concretely, of course, the scope of the present invention is not limited to the range of an Example. First, the preparation examples of the novel benzopyran derivatives used in the present invention will be described, followed by the results of pharmacological tests of the compounds of the present invention.
[137] Reference Example 1 Synthesis of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one
[138] 2.24 g (0.02 mol) of t-butoxy potassium was dissolved in 4 ml of dimethylformamide (hereinafter referred to as DMF), and 3-ethoxy-4,5-dihydroxy- dissolved in 16 ml of DMF in this solution. 2.22 g (0.01 mol) of 2H-1-benzopyran-2-one was added dropwise at 15 to 25 ° C, and stirring was continued for 30 minutes.
[139] 1.67 g (0.01 mol) of 2-bromoethyl acetate was added to this reaction liquid, and stirring was continued at the same temperature for 3 hours. The reaction solution was added to 105 ml of 3N hydrochloric acid, extracted twice with 50 ml of ethyl acetate, and the extract was dried over magnesium sulfate. The ethyl acetate solution was filtered off, and the filtrate was concentrated under reduced pressure to give 4.86 g of crude product. The crude product obtained was purified by silica gel column chromatography (eluent solvent: hexane / ethyl acetate = 2/1) to give 1.89 g of the title compound. (Yield 71%)
[140] ¹ H-NMR (CDCl ₃ , δ-TMS): 9.31 (bs, 1H), 6.70 to 7.40 (m, 3H), 4.43 (t, 2H, J = 5.0 Hz), 4.22 (t, 2H, J = 5.0 Hz), 4.10 (q, 2H, J = 6.0 Hz), 2.12 (s, 3H), 1.27 (t, 3H, J = 7.0 Hz)
[141] IR (KBr, cm ^-1 ): 3300, 3005, 1725, 1600, 1230
[142] Elemental Analysis Value: As C ₁₅ H ₁₆ O ₇ ,
[143] Calculated (%): C 58.44; H5.23; O36.33
[144] Found (%): C58.39; H5.22; O36.39
[145] Example 1 Synthesis of 3-ethoxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (2))
[146] 3.08 g (0.01 mol) of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one are added to 20 ml of 1N sodium hydroxide ethanol solution, and room temperature Stirred for 30 minutes.
[147] The reaction solution was neutralized in 105 ml of 0.2 ml of hydrochloric acid, and then extracted with ethyl acetate. The crude product obtained by concentrating the organic layer under reduced pressure was purified by silica gel column chromatography (eluent: hexane / acetone = 2/1), and then recrystallized (recrystallized solvent: ethyl acetate / hexane = 3/10), 2.36 g of the title compound were obtained. (Yield 88%)
[148] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[149] 9.27 (bs, 1H), 6.70-7.40 (m, 3H), 4.86 (bs, 1H), 4.16 (t, 2H, J = 5.0 Hz), 4.08 (q, 2H, J = 6.0 Hz), 3.77 (t , 2H, J = 5.0 Hz), 1.25 (t, 3H, J = 7.0 Hz)
[150] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[151] Elemental Analysis Value: As C ₁₃ H ₁₄ O ₆
[152] Calculated (%): C 58.64; H5.30; O36.06
[153] Found (%): C58.59; H5.40; O36.01
[154] Example 2 Synthesis of 3-butoxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (5))
[155] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mol of 3-butoxy-4,5-dihydroxy- 3-butoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2 in the same manner as in Reference Example 1 except that 2H-1-benzopyran-2-one was used. -Got on.
[156] In Example 1, the same mole of 3-butoxy- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that 4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[157] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[158] 9.27 (bs, 1H), 6.70-7.40 (m, 3H), 4.86 (bs, 1H), 4.07 (t, 2H, J = 6.0 Hz), 3.88 (t, 2H, J = 5.0 Hz), 3.77 (t , 2H, J = 6.0 Hz), 1.30-1.80 (m, 4H), 0.86 (t, 3H, J = 7.0 Hz)
[159] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[160] Elemental Analysis Value: As C ₁₅ H ₁₈ O ₆
[161] Calculated (%): C 61.21; H6.17; O32.62
[162] Found (%): C 61.15; H6.26; O32.59
[163] Example 3 Synthesis of 3-hexyloxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (8))
[164] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-hexyloxy-4, 5-dihydroxy-2H- Except using 1-benzopyran-2-one, it carried out similarly to the reference example 1, and 3-hexyloxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2 -Got on.
[165] In Example 1, the same mole of 3-hexyloxy-4- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[166] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[167] 9.29 (bs, 1H), 6.70-7.40 (m, 3H), 4.90 (bs, 1H), 4.07 (t, 2H, J = 6.0 Hz), 3.87 (t, 2H, J = 5.0 Hz), 3.75 (t , 2H, J = 6.0Hz), 1.30-1.80 (m, 8H), 0.86 (t, 3H, J = 7.0Hz)
[168] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[169] Elemental Analysis Value: As C ₁₇ H ₂₂ O ₆
[170] Calculated (%): C 63.34; H6.88; O29.79
[171] Found (%): C63.40; H6.91; O29.69
[172] Example 4 Synthesis of [3- (4-Methylpentyloxy) -4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (12)) ]
[173] In Reference Example 1, the same mole of 3- (4-methylpentyloxy) -4,5-dihydro instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3- (4-methylpentyloxy) -4-hydroxy-5- (2-acetoxyethoxy) -2H as in Reference Example 1, except that hydroxy-2H-1-benzopyran-2-one was used. -1-benzopyran-2-one was obtained.
[174] Example 1, instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one, the same mole of 3- (4-methylpentyloxy The title compound was obtained in the same manner as in Example 1 except that there was used) -4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one.
[175] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[176] 9.31 (bs, 1H), 6.70-7.40 (m, 3H), 4.86 (bs, 1H), 4.05 (t, 2H, J = 6.0 Hz), 3.85 (t, 2H, J = 5.0 Hz), 3.78 (t , 2H, J = 6.0Hz), 1.20-1.80 (m, 5H), 0.87 (d, 6H, J = 3.0Hz)
[177] IR (KBr, cm ^-1 ): 3300, 3000, 1660, 1600, 1230
[178] Elemental Analysis Value: As C ₁₇ H ₂₂ O ₆
[179] Calculated (%): C 63.34; H6.88; O29.79
[180] Found (%): C63.30; H6.81; O29.89
[181] Example 5 Synthesis of 3-octyloxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (14))
[182] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4,5-dihydroxy-2H-1 3-octyloxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used. Got it.
[183] In Example 1, 3-octyloxy-4-hydride in the same mole instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[184] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[185] 9.31 (bs, 1H), 6.70-7.40 (m, 3H), 4.90 (bs, 1H), 4.06 (t, 2H, J = 6.0 Hz), 3.89 (t, 2H, J = 5.0 Hz), 3.76 (t , 2H, J = 6.0Hz), 1.20-1.80 (m, 12H), 0.87 (t, 3H, J = 6.0Hz)
[186] IR (KBr, cm ^-1 ): 3300, 3005, 1660, 1610, 1230
[187] Elemental Analysis Value: as C ₁₉ H ₂₆ O ₆
[188] Calculated (%): C 65.12; H7.48; O27.40
[189] Found (%): C 65.02; H7.50; O27.48
[190] Example 6 Synthesis of 3-geranyloxy-4-hydroxy-5- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (24))
[191] In Reference Example 1, the same mole of 3-geranyloxy-4,5-dihydroxy-2H- in place of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one Except for using 1-benzopyran-2-one as in Reference Example 1, 3-geranyloxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2- Got on.
[192] In Example 1, the same mole of 3-geranyloxy-4- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[193] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[194] 9.30 (bs, 1H), 6.70 to 7.40 (m, 3H), 5.40 (m, 1H), 5.25 (m, 1H), 5.10 (m, 1H), 4.88 (bs, 1H), 4.23 (m, 2H) , 4.05 (t, 2H, J = 6.0 Hz), 3.78 (t, 2H, J = 6.0 Hz), 1.50-2.15 (m, 13H)
[195] IR (KBr, cm ^-1 ): 3300, 3005, 1660, 1610, 1230
[196] Elemental Analysis Value: as C ₂₁ H ₂₆ O ₆
[197] Calculated (%): C 67.36; H7.00; O25.64
[198] Found (%): C67.31; H6.97; O25.72
[199] Example 7 Synthesis of 3-butoxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (28))
[200] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-butoxy-4,5-dihydroxy-2H-1 3-Butoxy-4-hydroxy-5- was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. (3-acetoxypropoxy) -2H-1-benzopyran-2-one was obtained.
[201] In Example 1, 3-butoxy-4-hydroxy of the same mole instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-5- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used.
[202] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[203] 9.27 (bs, 1H), 6.70-7.40 (m, 3H), 4.89 (bs, 1H), 3.90-4.00 (m, 4H), 3.70 (t, 2H, J = 6.0 Hz), 1.30-1.95 (m, 6H), 0.85 (t, 3H, J = 7.0 Hz)
[204] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[205] Elemental Analysis Value: As C ₁₆ H ₂₀ O ₆
[206] Calculated (%): C 62.32; H6.54 .; O31.14
[207] Found (%): C 62.36; H6.63; O31.01
[208] Example 8 Synthesis of 3-hexyloxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (29))
[209] In Reference Example 1, the same mole of 3-hexyloxy-4,5-dihydroxy-2H- in place of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one Except for using 1-benzopyran-2-one and using 3-bromopropyl acetate instead of 2-bromoethyl acetate, 3-hexyloxy-4-hydroxy- as in Reference Example 1 5- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was obtained.
[210] In Example 1, the same mole of 3-hexyloxy-4- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that hydroxy-5- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used.
[211] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[212] 9.29 (bs, 1H), 6.70-7.40 (m, 3H), 4.90 (bs, 1H), 3.90-4.00 (m, 4H), 3.70 (t, 2H, J = 6.0 Hz), 1.20-1.95 (m, 10H), 0.87 (t, 3H, J = 7.0 Hz)
[213] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[214] Elemental Analysis Value: as C ₁₈ H ₂₄ O ₆
[215] Calculated (%): C64.27; H7.19; O28.54
[216] Found (%): C64.35; H7.22; O28.43
[217] Example 9 Synthesis of 3-octyloxy-4-hydroxy-5- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (31))
[218] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4,5-dihydroxy-2H-1 3-octyloxy-4-hydroxy-5- was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. (3-acetoxypropoxy) -2H-1-benzopyran-2-one was obtained.
[219] In Example 1, instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4-hydroxy The title compound was obtained in the same manner as in Example 1 except that oxy-5- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used.
[220] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[221] 9.30 (bs, 1H), 6.70-7.40 (m, 3H), 4.87 (bs, 1H), 3.90-4.00 (m, 4H), 3.72 (t, 2H, J = 6.0 Hz), 1.20-1.95 (m, 14H), 0.89 (t, 3H, J = 7.0 Hz)
[222] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[223] Elemental Analysis Value: As C ₂₀ H ₂₈ O ₆
[224] Calculated (%): C 65.91; H7.74; O26.34
[225] Found (%): C 65.84; H7.83; O26.33
[226] Example 10 Synthesis of 3-ethoxy-4-hydroxy-5- (3-hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (36))
[227] In Reference Example 1, except that 3-bromobutyl acetate was used instead of 2-bromoethyl acetate, 3-ethoxy-4-hydroxy-5- (3-acetoxybutoxy was used in the same manner as in Reference Example 1. ) -2H-1-benzopyran-2-one was obtained.
[228] Example 1, 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one, instead of 3-ethoxy-4-hydroxy The title compound was obtained in the same manner as in Example 1 except that oxy-5- (3-acetoxybutoxy) -2H-1-benzopyran-2-one was used.
[229] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[230] 9.28 (bs, 1H), 6.70-7.40 (m, 3H), 4.83 (bs, 1H), 4.19 (t, 2H, J = 5.0 Hz), 4.00 (q, 2H, J = 6.0 Hz), 3.78 (t , 2H, J = 5.0 Hz), 1.40-1.75 (m, 4H), 1.23 (t, 3H, J = 7.0 Hz)
[231] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[232] Elemental Analysis Value: As C ₁₅ H ₁₈ O ₆
[233] Calculated (%): C 61.21; H6.17; O32.62
[234] Found (%): C 61.10; H6.21; O32.69
[235] Example 11 Synthesis of 3-butoxy-4-hydroxy-5- (3-hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (37))
[236] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-butoxy-4,5-dihydroxy-2H-1 3-Butoxy-4-hydroxy-5- was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 3-bromobutyl acetate was used instead of 2-bromoethyl acetate. (3-acetoxybutoxy) -2H-1-benzopyran-2-one was obtained.
[237] In Example 1, the same mole of 3-butoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-5- (3-acetoxybutoxy) -2H-1-benzopyran-2-one was used.
[238] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[239] 9.31 (bs, 1H), 6.70-7.40 (m, 3H), 4.85 (bs, 1H), 3.90-4.00 (m, 4H), 3.73 (t, 2H, J = 6.0 Hz), 1.30-1.95 (m, 8H), 0.85 (t, 3H, J = 7.0 Hz)
[240] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[241] Elemental Analysis Value: As C ₁₇ H ₂₂ O ₆
[242] Calculated (%): C 63.34; H6.88; O29.78
[243] Found (%): C63.36; H6.97; O29.67
[244] Reference Example 2 [3-hexyloxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one synthesis]
[245] 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 2.78 dissolved in 16 ml of DMF in a solution in which 2.24 g (0.02 mol) of t-butoxy potassium was dissolved in 4 ml of DMF. After dropping g (0.01 mol) at 15-25 degreeC, stirring was continued for 30 minutes.
[246] 2.86 g (0.01 mol) of 2,2-dimethyl-1,3-dioxolan-4-ylmethylparatoluenesulfonate was added to this reaction liquid, and stirring was continued at the same temperature for 3 hours. The reaction solution was added to 105 ml of hydrochloric acid at a concentration of 3 mol / L, extracted twice with 50 ml of ethyl acetate, and the extract was dried over magnesium sulfate. The filtrate of the extract was concentrated under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2/1) to obtain 2.35 g of the title compound. (Yield 60%)
[247] ¹ H-NMR (CDC1 ₃ , δ-TMS)
[248] 9.20 (bs, 1H), 6.70-7.40 (m, 3H), 4.52 (t, 2H, J = 5.2 Hz), 3.90-4.21 (m, 5H), 1.75 (m, 2H), 1.48 (s, 3H) , 1.42 (s, 3H), 1.20-1.41 (m, 6H), 0.87 (t, 3H, J = 7.0 Hz)
[249] IR (KBr, cm ^-1 ): 3300, 3005, 1725, 1600, 1230
[250] Elemental Analysis Value: As C ₂₁ H ₂₈ O ₇ .
[251] Calculated (%): C64.27; H7.19; O28.54
[252] Found (%): C64.23; H7.28; O28.49
[253] Example 12 Synthesis of 3-hexyloxy-4-hydroxy-5- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (46))
[254] 3.92 g (0.01 mol) of 3-hexyloxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one 40 ml of 80% acetic acid solution was added, and stirring was continued at 60 ° C for 4 hours.
[255] The reaction solution was concentrated under reduced pressure, 40 ml of water was added to the concentrate, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure and the crude product obtained was recrystallized from methanol to give 1.87 g of the title compound. (Yield 53%)
[256] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[257] 9.33 (bs, 1H), 6.70 to 7.40 (m, 3H), 5.00 (s, 1H), 4.70 (s, 1H), 3.81 to 4.11 (m, 5H), 3.45 (s, 2H), 1.69 (m, 2H), 1.18-1.40 (m, 6H), 0.86 (t, 3H, J = 7.0 Hz)
[258] IR (KBr, cm ^-1 ): 3420, 3005, 1680, 1610, 1260
[259] Elemental Analysis Value: as C ₁₈ H ₂₄ O ₇
[260] Calculated (%): C 61.35; H6.86; O31.78
[261] Found (%): C 61.28; H6.88; O31.84
[262] Example 13 Synthesis of 3-butoxy-4-hydroxy-5- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (45))
[263] In Reference Example 2, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-butoxy-4,5-dihydroxy-2H- 3-butoxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) in the same manner as in Reference Example 2, except that 1-benzopyran-2-one was used. -2H-1-benzopyran-2-one was obtained.
[264] In Example 12, instead of 3-hexyloxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one , Except that the same moles of 3-butoxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one were used The title compound was obtained in the same manner as in Example 12.
[265] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[266] 9.31 (bs, 1H), 6.70-7.40 (m, 3H), 5.01 (s, 1H), 4.70 (s, 1H), 3.81-4.11 (m, 5H), 3.45 (s, 2H), 1.18-1.40 ( m, 4H), 0.86 (t, 3H, J = 7.0 Hz)
[267] IR (KBr, cm ^-1 ): 3420, 3005, 1680, 1610, 1260
[268] Elemental Analysis Value: as C ₁₆ H ₂₀ O ₇
[269] Calculated (%): C 59.25; H6.22; O34.53
[270] Found (%): C59.21; H6.15; O34.64
[271] Reference Example 3 Synthesis of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one
[272] In Reference Example 2, the title compound was prepared in the same manner as in Reference Example 2, except that the same mole of ethyl bromoacetate was used instead of 2,2-dimethyl-1 and 3-dioxolan-4-ylmethylparatoluenesulfonate. Got it.
[273] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[274] 9.27 (bs, 1H), 6.70-7.40 (m, 3H), 4.90 (s, 2H), 3.81-4.11 (m, 4H), 1.69 (m, 2H), 1.20-1.40 (m, 9H), 0.86 ( t, 3H, J = 7.0 Hz)
[275] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[276] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[277] Calculated (%): C 62.62; H6.64; O30.73
[278] Found (%): C 62.53; H6.71; O30.76
[279] Example 14 Synthesis of 3-hexyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (65))
[280] 1 mol / L hydroxide under ice-cooling with 3.64 g (0.01 mol) of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one added 25 ml of ethanol 25 ml of aqueous sodium solution was added, and stirring was continued at room temperature for 4 hours. The reaction solution was added to 26 ml of hydrochloric acid at a concentration of 1 mol / L, extracted twice with 50 ml of ethyl acetate, and the extract was dried over magnesium sulfate. After filtering the ethyl acetate solution, the filtrate was concentrated under reduced pressure, and the crude product obtained was recrystallized from methanol to obtain 2.49 g of the title compound. (Yield 74%)
[281] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[282] 11.02 (bs, 1H), 9.27 (bs, 1H), 6.70-7.40 (m, 3H), 4.88 (s, 2H), 3.88 (t, 2H, J = 5.0 Hz), 1.69 (m, 2H), 1.20 -1.40 (m, 6H), 0.86 (t, 3H, J = 7.0 Hz)
[283] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[284] Elemental Analysis Value: as C ₁₇ H ₂₀ O ₇
[285] Calculated (%): C 60.71; H5.99; O33.30
[286] Found (%): C 60.67; H6.11; O33.22
[287] Example 15 Synthesis of 3-ethoxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (59))
[288] In Reference Example 3, the same mole of 3-ethoxy-4,5-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-Ethoxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used.
[289] In Example 14, the same mole of 3-ethoxy-4-hydroxy- instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[290] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[291] 11.12 (bs, 1H), 9.29 (bs, 1H), 6.70-7.40 (m, 3H), 4.88 (s, 2H), 4.08 (q, 2H, J = 6.0 Hz), 1.25 (t, 3H, J = 7.0 Hz)
[292] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[293] Elemental Analysis Value: as C ₁₃ H ₁₂ O ₇
[294] Calculated (%): C 55.72; H4.32; O39.97
[295] Found (%): C55.64; H4.26; O40.10
[296] Example 16 Synthesis of 3-butoxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (62))
[297] In Reference Example 3, the same mole of 3-butoxy-4,5-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one A 3-butoxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used. .
[298] In Example 14, the same mole of 3-butoxy-4-hydroxy- as an alternative to 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[299] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[300] 11.08 (bs, 1H), 9.30 (bs, 1H), 6.70-7.40 (m, 3H), 4.88 (s, 2H), 3.98 (t, 2H, J = 6.0 Hz), 1.30-1.95 (m, 4H) , 0.85 (t, 3H, J = 7.0 Hz)
[301] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[302] Elemental Analysis Value: as C ₁₅ H ₁₆ O ₇
[303] Calculated (%): C 58.44; H5.23; O36.33
[304] Found (%): C 58.45; H5.29; O36.26
[305] Example 17 Synthesis of 3-octyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (71))
[306] In Reference Example 3, the same mole of 3-octyloxy-4,5-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one A 3-octyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used. .
[307] In Example 14, the same mole of 3-octyloxy-4-hydroxy- in place of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[308] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[309] 11.06 (bs, 1H), 9.26 (bs, 1H), 6.70-7.40 (m, 3H), 4.87 (s, 2H), 3.99 (t, 2H, J = 6.0 Hz), 1.30-1.95 (m, 12H) , 0.85 (t, 3H, J = 7.0 Hz)
[310] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[311] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[312] Calculated (%): C 62.62; H6.64; O30.73
[313] Found (%): C 62.69; H6.53; O30.78
[314] Example 18 Synthesis of 3-geranyloxy-4-hydroxy-5-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (81))
[315] In Reference Example 3, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-geranyloxy-4,5-dihydroxy-2H Except having used -1-benzopyran-2-one, it carried out similarly to the reference example 3, 3-geranyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2 -Got on.
[316] In Example 14, the same mole of 3-geranyloxy-4-hydroxy instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 5-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[317] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[318] 11.11 (bs, 1H), 9.28 (bs, 1H), 6.70-7.40 (m, 3H), 5.40 (m, 1H), 5.25 (m, 1H), 5.10 (m, 1H), 4.87 (s, 2H) , 4.23 (m, 2H), 4.05 (t, 2H, J = 6.0 Hz), 3.78 (t, 2H, J = 6.0 Hz), 1.50-2.15 (m, 13H)
[319] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[320] Elemental Analysis Value: as C ₂₁ H ₂₄ O ₇ .
[321] Calculated (%): C64.93; H6.23; O28.84
[322] Found (%): C64.87; H6.31; O28.82
[323] Example 19 Synthesis of 3-butoxy-4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (85))
[324] In Reference Example 3, the same mole of 3-butoxy-4,5-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-Butoxy-4-hydroxy-5- was used in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used and ethyl 3-bromopropionate was used instead of ethyl bromoacetate. (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[325] In Example 14, the same mole of 3-butoxy-4-hydroxy- as an alternative to 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 5- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used.
[326] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[327] 11.10 (bs, 1H), 9.27 (bs, 1H), 6.70-7.40 (m, 3H), 4.45 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H, J = 6.0 Hz), 3.18 (t , 2H, J = 5.0Hz), 1.30-1.95 (m, 4H), 0.87 (t, 3H, J = 7.0Hz)
[328] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[329] Elemental Analysis Value: As C ₁₆ H ₁₈ O ₇
[330] Calculated (%): C 59.62; H5.63; O34.75
[331] Found (%): C59.66; H5.51; O34.83
[332] Example 20 Synthesis of 3-hexyloxy-4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (86))
[333] In Reference Example 3, 3-hexyloxy-4-hydroxy-5- (2-ethoxy was prepared in the same manner as in Reference Example 3 except that the same mole of ethyl 3-bromopropionate was used instead of ethyl bromoacetate. Carbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[334] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 5-5- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used.
[335] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[336] 11.13 (bs, 1H), 9.27 (bs, 1H), 6.70-7.40 (m, 3H), 4.45 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H, J = 6.0 Hz), 3.18 (t , 2H, J = 5.0 Hz), 1.69 (m, 2H), 1.30-1.95 (m, 8H), 0.88 (t, 3H, J = 7.0 Hz)
[337] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[338] Elemental Analysis Value: as C ₁₈ H ₂₂ O ₇
[339] Calculated (%): C 61.70; H6.33; O31.97
[340] Found (%): C 61.58; H6.37; O32.05
[341] Example 21 Synthesis of 3-octyloxy-4-hydroxy-5- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (87))
[342] In Reference Example 3, the same mole of 3-octyloxy-4,5-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-octyloxy-4-hydroxy-5- was obtained in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used and ethyl 3-bromopropionate was used instead of ethyl bromoacetate. (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[343] In Example 14, the same mole of 3-octyloxy-4-hydroxy- in place of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 5- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used.
[344] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[345] 11.12 (bs, 1H), 9.28 (bs, 1H), 6.70-7.40 (m, 3H), 4.41 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H, J = 6.0 Hz), 3.19 (t , 2H, J = 5.0 Hz), 1.69 (m, 2H), 1.30-1.95 (m, 12H), 0.88 (t, 3H, J = 7.0 Hz)
[346] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[347] Elemental Analysis Value: as C ₂₀ H ₂₆ O ₇
[348] Calculated (%): C 63.48; H6.93; O29.60
[349] Found (%): C 63.51; H6.82; O29.67
[350] Example 22 Synthesis of 3-hexyloxy-4-hydroxy-5- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound (93))
[351] In Reference Example 3, 3-hexyloxy-4-hydroxy-5- (3-ethoxy Carbonylpropoxy) -2H-1-benzopyran-2-one was obtained.
[352] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -5- (3-ethoxycarbonylpropoxy) -2H-1-benzopyran-2-one.
[353] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[354] 11.12 (bs, 1H), 9.28 (bs, 1H), 6.70-7.40 (m, 3H), 4.41 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H, J = 6.0 Hz), 2.23 (t , 2H, J = 5.0Hz), 1.30-2.00 (m, 10H), 0.88 (t, 3H, J = 7.0Hz)
[355] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[356] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[357] Calculated (%): C 62.62; H6.64; O30.73
[358] Found (%): C 62.53; H6.67; O30.80
[359] Example 23 Synthesis of 3-hexyloxy-4-hydroxy-5- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (99))
[360] In Reference Example 3, 3-hexyloxy-4-hydroxy-5- (4-ethoxy was prepared in the same manner as in Reference Example 3 except that the same molar amount of 5-bromopentane carbonate was used instead of ethyl bromoacetate. Carbonylbutoxy) -2H-1-benzopyran-2-one was obtained.
[361] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 5-5- (4-ethoxycarbonylbutoxy) -2H-1-benzopyran-2-one was used.
[362] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[363] 11.11 (bs, 1H), 9.29 (bs, 1H), 6.70-7.40 (m, 3H), 4.40 (t, 2H, J = 5.0 Hz), 3.99 (t, 2H, J = 6.0 Hz), 2.23 (t , 2H, J = 5.0 Hz), 1.30-2.00 (m, 12H), 0.88 (t, 3H, J = 7.0 Hz)
[364] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[365] Elemental Analysis Value: as C ₂₀ H ₂₆ O ₇
[366] Calculated (%): C 63.48; H6.93; O29.60
[367] Found (%): C63.46; H6.85; O29.69
[368] Example 24 Synthesis of 3-ethoxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (103))
[369] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-ethoxy-4,6-hydroxy-2H-1-benzo Except having used pyran-2-one, it carried out similarly to Reference Example 1, and obtained 3-ethoxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one.
[370] In Example 1, the same mole of 3-butoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[371] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[372] 9.98 (bs, 1H), 6.80-7.40 (m, 3H), 4.87 (bs, 1H), 4.14 (t, 2H, J = 5.0 Hz), 4.08 (q, 2H, J = 6.0 Hz), 3.77 (t , 2H, J = 5.0 Hz), 1.25 (t, 3H, J = 7.0 Hz)
[373] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[374] Elemental Analysis Value: As C ₁₃ H ₁₄ O ₆
[375] Calculated (%): C 58.64; H5.30; O36.06
[376] Found (%): C58.68; H5.22; O36.10
[377] Example 25 Synthesis of 3-butoxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (106))
[378] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-butoxy-4,6-dihydroxy-2H-1 A 3-butoxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used. Got it.
[379] In Example 1, the same mole of 3-butoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[380] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[381] 9.96 (bs, 1H), 6.80-7.20 (m, 3H), 4.85 (bs, 1H), 4.09 (t, 2H, J = 6.0 Hz), 3.84 (t, 2H, J = 5.0 Hz), 3.77 (t , 2H, J = 6.0Hz), 1.30-1.80 (m, 4H), 0.88 (t, 3H, J = 7.0Hz)
[382] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[383] Elemental Analysis Value: As C ₁₅ H ₁₈ O ₆
[384] Calculated (%): C 61.21; H6.17; O32.62
[385] Found (%): C 61.30; H6.23, O32.47
[386] Example 26 Synthesis of 3-hexyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (109))
[387] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-hexyloxy-4,6-dihydroxy-2H- Except having used 1-benzopyran-2-one, it carried out like the reference example 1 and 3-hexyloxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2- Got on.
[388] In Example 1, the same mole of 3-hexyloxy-4- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[389] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[390] 10.02 (bs, 1H), 6.80-7.20 (m, 3H), 4.91 (bs, 1H), 4.07 (t, 2H, J = 6.0 Hz), 3.90 (t, 2H, J = 5.0 Hz), 3.75 (t , 2H, J = 6.0Hz), 1.30-1.80 (m, 8H), 0.87 (t, 3H, J = 7.0Hz)
[391] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[392] Elemental Analysis Value: As C ₁₇ H ₂₂ O ₆
[393] Calculated (%): C 63.34; H6.88; O29.79
[394] Found (%): C 63.28; H6.82; O29.90
[395] Example 27 Synthesis of [3- (4-Methylpentyloxy) -4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (11)) ]
[396] In Reference Example 1, the same mole of 3- (4-methylpentyloxy) -4,6-dihydro instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3- (4-methylpentyloxy) -4-hydroxy-6- (2-acetoxyethoxy) -2H as in Reference Example 1, except that oxy-2H-1-benzopyran-2-one was used. -1-benzopyran-2-one was obtained.
[397] Example 1, instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one, the same mole of 3- (4-methylpentyloxy The title compound was obtained in the same manner as in Example 1 except that there was used) -4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one.
[398] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[399] 9.98 (bs, 1H), 6.80-7.20 (m, 3H), 4.85 (bs, 1H), 4.07 (t, 2H, J = 6.0 Hz), 3.83 (t, 2H, J = 5.0 Hz), 3.77 (t , 2H, J = 6.0Hz), 1.20-1.80 (m, 5H), 0.87 (d, 6H, J = 3.0Hz)
[400] IR (KBr, cm ^-1 ): 3300, 3000, 1660, 1600, 1230
[401] Elemental Analysis Value: As C ₁₇ H ₂₂ O ₆
[402] Calculated (%): C 63.34; H6.88; O29.79
[403] Found (%): C 63.45; H6.91; O29.64
[404] Example 28 Synthesis of 3-octyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (115))
[405] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4,6-dihydroxy-2H-1 A 3-octyloxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used. Got it.
[406] In Example 1, instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4-hydroxy The title compound was obtained in the same manner as in Example 1 except that oxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[407] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[408] 9.96 (bs, 1H), 6.80-7.20 (m, 3H), 4.89 (bs, 1H), 4.06 (t, 2H, J = 6.0 Hz), 3.87 (t, 2H, J = 5.0 Hz), 3.79 (t , 2H, J = 6.0Hz), 1.20-1.80 (m, 12H), 0.88 (d, 3H, J = 6.0Hz)
[409] IR (KBr, cm ^-1 ): 3300, 3005, 1660, 1610, 1230
[410] Elemental Analysis Value: as C ₁₉ H ₂₆ O ₆
[411] Calculated (%): C 65.12; H7.48; O27.40
[412] Found (%): C64.99; H7.54; O27.47
[413] Example 29 Synthesis of 3-geranyloxy-4-hydroxy-6- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (125))
[414] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-geranyloxy-4,6-dihydroxy-2H- Except having used 1-benzopyran-2-one, it carried out similarly to the reference example 1, and 3-geranyloxy-4-hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2- Got on.
[415] In Example 1, the same mole of 3-geranyloxy-4- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that hydroxy-6- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[416] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[417] 9.98 (bs, 1H), 6.80 to 7.20 (m, 3H), 5.39 (m, 1H), 5.26 (m, 1H), 5.10 (m, 1H), 4.89 (bs, 1H), 4.23 (m, 2H) , 4.04 (t, 2H, J = 6.0 Hz), 3.76 (t, 2H, J = 6.0 Hz), 1.50-2.15 (m, 13H)
[418] IR (KBr, cm ^-1 ): 3300, 3005, 1660, 1610, 1230
[419] Elemental Analysis Value: as C ₂₁ H ₂₆ O ₆
[420] Calculated (%): C 67.36; H7.00; O25.64
[421] Found (%): C67.42; H6.91; O25.67
[422] Example 30 Synthesis of 3-butoxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (129))
[423] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-butoxy-4,6-dihydroxy-2H-1 3-Butoxy-4-hydroxy-6- (3 was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 3-bromopropyl acetate was used instead of bromoethyl acetate. -Acetoxypropoxy) -2H-1-benzopyran-2-one was obtained.
[424] In Example 1, the same mole of 3-butoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-6- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used.
[425] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[426] 9.99 (bs, 1H), 6.80-7.20 (m, 3H), 4.89 (bs, 1H), 3.90-4.00 (m, 4H), 3.71 (t, 2H, J = 6.0 Hz), 1.30-1.95 (m, 6H), 0.87 (t, 3H, J = 7.0 Hz)
[427] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[428] Elemental Analysis Value: As C ₁₆ H ₂₀ O ₆
[429] Calculated (%): C 62.32; H6.54; O31.14
[430] Found (%): C 62.37; H6.42; O31.21
[431] Example 31 Synthesis of 3-hexyloxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (130))
[432] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-hexyloxy-4,6-dihydroxy-2H- 3-hexyloxy-4-hydroxy-6 as in Reference Example 1, except that 1-benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. -(3-acetoxypropoxy) -2H-1-benzopyran-2-one was obtained.
[433] In Example 1, the same mole of 3-hexyloxy-4- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that hydroxy-6- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used.
[434] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[435] 10.02 (bs, 1H), 6.80-7.20 (m, 3H), 4.87 (bs, 1H), 3.90-4.00 (m, 4H), 3.70 (t, 2H, J = 6.0 Hz), 1.20-1.95 (m, 10H), 0.86 (t, 3H, J = 7.0 Hz)
[436] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[437] Elemental Analysis Value: as C ₁₈ H ₂₄ O ₆
[438] Calculated (%): C64.27; H7.19; O28.54
[439] Found (%): C64.31; H7.26; O28.43
[440] Example 32 Synthesis of 3-octyloxy-4-hydroxy-6- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (132))
[441] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4,6-dihydroxy-2H-1 A 3-octyloxy-4-hydroxy-6- was prepared in the same manner as in Reference Example 1 except that 3-benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. (3-acetoxypropoxy) -2H-1-benzopyran-2-one was obtained.
[442] In Example 1, instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4-hydroxy The title compound was obtained in the same manner as in Example 1 except that oxy-6- (3-acetoxypropoxy) -2H-1-benzopyran-2-one was used.
[443] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[444] 9.99 (bs, 1H), 6.80-7.20 (m, 3H), 4.89 (bs, 1H), 3.90-4.00 (m, 4H), 3.71 (t, 2H, J = 6.0 Hz), 1.20-1.95 (m, 14H), 0.89 (t, 3H, J = 7.0 Hz)
[445] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[446] Elemental Analysis Value: As C ₂₀ H ₂₈ O ₆
[447] Calculated (%): C 65.91; H7.74; O26.34
[448] Found (%): C66.02; H7.69; O26.29
[449] Example 33 Synthesis of 3-ethoxy-4-hydroxy-6- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (137))
[450] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-ethoxy-4,6-dihydroxy-2H-1 Except for using -benzopyran-2-one, and instead of bromoethyl acetate, 4-bromobutyl acetate was prepared as in Reference Example 1, 3-ethoxy-4-hydroxy-6- (4- Acetoxybutoxy) -2H-1-benzopyran-2-one was obtained.
[451] In Example 1, the same mole of 3-ethoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-6- (4-acetoxybutoxy) -2H-1-benzopyran-2-one was used.
[452] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[453] 9.98 (bs, 1H), 6.80-7.20 (m, 3H), 4.84 (bs, 1H), 4.17 (t, 2H, J = 5.0 Hz), 3.99 (q, 2H, J = 6.0 Hz), 3.78 (t , 2H, J = 5.0Hz), 1.40-1.75 (m, 4H), 1.22 (t, 3H, J = 7.0Hz)
[454] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[455] Elemental Analysis Value: As C ₁₅ H ₁₈ O ₆
[456] Calculated (%): C 61.21; H6.17; O32.62
[457] Found (%): C 61.15; H6.28; O32.57
[458] Example 34 Synthesis of 3-butoxy-4-hydroxy-6- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (138))
[459] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-butoxy-4,6-dihydroxy-2H-1 3-Butoxy-4-hydroxy-6- (4 was used in the same manner as in Reference Example 1, except that 4-benzopyran-2-one was used and 4-bromobutyl acetate was used instead of bromoethyl acetate. -Acetoxybutoxy) -2H-1-benzopyran-2-one was obtained.
[460] In Example 1, the same mole of 3-butoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-6- (4-acetoxybutoxy) -2H-1-benzopyran-2-one was used.
[461] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[462] 9.97 (bs, 1H), 6.80-7.20 (m, 3H), 4.86 (bs, 1H), 3.90-4.00 (m, 4H), 3.72 (t, 2H, J = 6.0 Hz), 1.30-1.95 (m, 8H), 0.86 (t, 3H, J = 7.0 Hz)
[463] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[464] Elemental Analysis Value: As C ₁₇ H ₂₂ O ₆
[465] Calculated (%): C 63.34; H6.88; O29.78
[466] Found (%): C 63.23; H6.93; O29.84
[467] (Reference Example 4) of [3-hexyloxy-4-hydroxy-6- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one synthesis]
[468] In Reference Example 2, the same mole of 3-hexyloxy-4,6-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as the Reference Example 2 except that -1-benzopyran-2-one was used.
[469] ¹ H-NMR (CDCl ₃ , δ-TMS):
[470] 9.99 (bs, 1H), 6.80-7.20 (m, 3H), 4.51 (t, 2H, J = 5.2 Hz), 3.90-4.21 (m, 5H), 1.75 (m, 2H), 1.48 (s, 3H) , 1.42 (s, 3H), 1.20-1.41 (m, 6H), 0.88 (t, 3H, J = 7.0 Hz)
[471] IR (KBr, cm ^-1 ): 3300, 3005, 1725, 1600, 1230
[472] Elemental Analysis Value: As C ₂₁ H ₂₈ O ₈ .
[473] Calculated (%): C64.27; H7.19; O28.54
[474] Found (%): C64.34; H7.21; O28.45
[475] Example 35 Synthesis of 3-hexyloxy-4-hydroxy-6- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (147))
[476] Instead of 3-hexyloxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one , 3-hexyloxy-4-hydroxy-6- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran of the same mole obtained in Reference Example 3 The title compound was obtained in the same manner as in Example 12 except that 2-one was used.
[477] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[478] 10.03 (bs, 1H), 6.80-7.20 (m, 3H), 4.98 (s, 1H), 4.71 (s, 1H), 3.81-4.11 (m, 5H), 3.45 (s, 2H), 1.70 (m, 2H), 1.18-1.40 (m, 6H). 0.86 (t, 3H, J = 7.0 Hz)
[479] IR (KBr, cm ^-1 ): 3420, 3005, 1680, 1610, 1260
[480] Elemental Analysis Value: as C ₁₈ H ₂₄ O ₇
[481] Calculated (%): C 61.35; H6.86; O31.78
[482] Found (%): C 61.40; H6.74; O31.86
[483] Example 36 Synthesis of 3-butoxy-4-hydroxy-6- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (146))
[484] In the Reference Example 2, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-butoxy-4,6-dihydroxy-2H- 3-butoxy-4-hydroxy-6- (2,2-dimethoxy-1,3-dioxolane-4-ethoxy was prepared in the same manner as in Reference Example 2 except that 1-benzopyran-2-one was used. ) -2H-1-benzopyran-2-one was obtained.
[485] In Example 2, instead of 3-butoxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-ethoxy) -2H-1-benzopyran-2-one, Example 2, except that 3-butoxy-4-hydroxy-6- (2,2-dimethyl-1,3-dioxolane-4-ethoxy) -2H-1-benzopyran-2-one was used The title compound was obtained in the same manner.
[486] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[487] 9.97 (bs, 1H), 6.80-7.20 (m, 3H), 5.01 (s, 1H), 4.69 (s, 1H), 3.81-4.11 (m, 5H), 3.44 (s, 2H), 1.18-1.40 ( m, 4H), 0.86 (t, 3H, J = 7.0 Hz)
[488] IR (KBr, cm ^-1 ): 3420, 3005, 1680, 1610, 1260
[489] Elemental Analysis Value: as C ₁₆ H ₂₀ O ₇
[490] Calculated (%): C 59.25; H6.22; O34.53
[491] Found (%): C59.18; H6.20; O34.62
[492] (Reference Example 5) [Synthesis of 3-hexyloxy-4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one]
[493] In Reference Example 3, the same mole of 3-hexyloxy-4,6-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as the Reference Example 3 except that -1-benzopyran-2-one was used.
[494] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[495] 9.99 (bs, 1H), 6.80-7.20 (m, 3H), 4.91 (s, 2H), 3.81-4.11 (m, 4H), 1.69 (m, 2H), 1.20-1.40 (m, 9H), 0.88 ( t, 3H, J = 7.0 Hz)
[496] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[497] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[498] Calculated (%): C 62.62; H6.64; O30.73
[499] Found (%): C 62.71; H6.60; O30.69
[500] Example 37 Synthesis of 3-hexyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (166))
[501] The same mole of 3-hexyloxy obtained in Reference Example 5 as in Example 14, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[502] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[503] 11.02 (bs, 1H), 9.99 (bs, 1H), 6.80-7.20 (m, 3H), 4.87 (s, 2H), 3.89 (t, 2H, J = 5.0 Hz), 1.69 (m, 2H), 1.20 -1.40 (m, 6H), 0.86 (t, 3H, J = 7.0 Hz)
[504] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[505] Elemental Analysis Value: as C ₁₇ H ₂₀ O ₇
[506] Calculated (%): C 60.71; H5.99; O33.30
[507] Found (%): C 60.79; H6.10; O33.11
[508] Example 38 Synthesis of 3-ethoxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (160))
[509] In Reference Example 3, the same mole of 3-ethoxy-4,6-dihydroxy-2H-1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-Ethoxy-4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3 except that -benzopyran-2-one was used.
[510] In Example 14, the same mole of 3-ethoxy-4-hydroxy- instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[511] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[512] 11.11 (bs, 1H), 10.01 (bs, 1H), 6.80-7.20 (m, 3H), 4.86 (s, 2H), 4.08 (q, 2H, J = 6.0 Hz), 1.26 (t, 3H, J = 7.0 Hz)
[513] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[514] Elemental Analysis Value: as C ₁₃ H ₁₂ O ₇
[515] Calculated (%): C 55.72; H4.32; O39.97
[516] Found (%): C55.76; H4.13; O40.11
[517] Example 39 Synthesis of 3-butoxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (163))
[518] In Reference Example 3, the same mole of 3-butoxy-4,6-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-butoxy-4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used.
[519] In Example 14, the same mole of 3-butoxy-4-hydroxy- as an alternative to 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[520] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[521] 11.08 (bs, 1H), 9.98 (bs, 1H), 6.80-7.20 (m, 3H), 4.89 (s, 2H), 3.96 (t, 2H, J = 6.0 Hz), 1.30-1.95 (m, 4H) , 0.86 (t, 3H, J = 7.0 Hz)
[522] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[523] Elemental Analysis Value: as C ₁₅ H ₁₆ O ₇
[524] Calculated (%): C 58.44; H5.23; O36.33
[525] Found (%): C58.35; H5.25; O36.40
[526] Example 40 Synthesis of 3-octyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (172))
[527] In Reference Example 3, the same mole of 3-octyloxy-4,6-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-Octyloxy-4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used.
[528] In Example 14, the same mole of 3-octyloxy-4-hydroxy- in place of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[529] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[530] 11.10 (bs, 1H), 9.98 (bs, 1H), 6.80-7.20 (m, 3H), 4.87 (s, 2H), 3.97 (t, 2H, J = 6.0 Hz), 1.30-1.95 (m, 12H) , 0.85 (t, 3H, J = 7.0 Hz)
[531] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[532] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[533] Calculated (%): C 62.62; H6.64; O30.73
[534] Found (%): C 62.56; H6.80; O30.64
[535] Example 41 Synthesis of 3-geranyloxy-4-hydroxy-6-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (182))
[536] In Reference Example 3, the same mole of 3-geranyloxy-4,6-dihydroxy-2H instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one A 3-geranyloxy-4-hydroxy-6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was prepared in the same manner as in Reference Example 3 except that -1-benzopyran-2-one was used. Got it.
[537] In Example 14, the same mole of 3-geranyloxy-4-hydroxy instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -6-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one.
[538] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[539] 11.16 (bs, 1H), 9.96 (bs, 1H), 6.80-7.20 (m, 3H), 5.39 (m, 1H), 5.24 (m, 1H), 5.10 (m, 1H), 4.87 (s, 2H) , 4.25 (m, 2H), 4.05 (t, 2H, J = 6.0 Hz), 3.79 (t, 2H, J = 6.0 Hz), 1.50-2.15 (m, 13H)
[540] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[541] Elemental Analysis Value: as C ₂₁ H ₂₄ O ₇ .
[542] Calculated (%): C64.93; H6.23; O28.84
[543] Found (%): C64.95; H6.13; O28.92
[544] Example 42 Synthesis of 3-butoxy-4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (186))
[545] In Reference Example 3, the same mole of 3-ethoxy-4,6-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one In the same manner as in Reference Example 3, except that 1-benzopyran-2-one was used and 3-bromopropionate acetate was used instead of ethyl bromoacetate, 3-ethoxy-4-hydroxy-6- ( 2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[546] In Example 14, the same mole of 3-butoxy-4-hydroxy- as an alternative to 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 6- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used.
[547] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[548] 11.14 (bs, 1H), 9.99 (bs, 1H), 6.80-7.20 (m, 3H), 4.43 (t, 2H, J = 5.0 Hz), 3.97 (t, 2H, J = 6.0 Hz), 3.18 (t , 2H, J = 5.0 Hz), 1.30-1.95 (m, 4H), 0.88 (t, 3H, J = 7.0 Hz)
[549] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[550] Elemental Analysis Value: As C ₁₆ H ₁₈ O ₇
[551] Calculated (%): C 59.62; H5.63; O34.75
[552] Found (%): C59.59; H5.57; O34.84
[553] Example 43 Synthesis of 3-hexyloxy-4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (187))
[554] In Reference Example 3, the same mole of 3-hexyloxy-4,6-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-hexyloxy-4-hydroxy-6- was used in the same manner as in Reference Example 3 except that -1-benzopyran-2-one was used, and 3-bromopropionate ethyl was used instead of ethyl bromoacetate. (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[555] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -6- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one.
[556] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[557] 11.12 (bs, 1H), 9.98 (bs, 1H), 6.80-7.20 (m, 3H), 4.46 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H, J = 6.0 Hz), 3.19 (t , 2H, J = 5.0 Hz), 1.69 (m, 2H), 1.30-1.95 (m, 8H), 0.87 (t, 3H, J = 7.0 Hz)
[558] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[559] Elemental Analysis Value: as C ₁₈ H ₂₂ O ₇
[560] Calculated (%): C 61.70; H6.33; O31.97
[561] Found (%): C 61.83; H6.21; O31.96
[562] Example 44 Synthesis of 3-octyloxy-4-hydroxy-6- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (188))
[563] In Reference Example 3, the same mole of 3-octyloxy-4,6-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-octyloxy-4-hydroxy-6- (2 was used in the same manner as in Reference Example 3, except that 1-benzopyran-2-one was used and ethyl 3-bromopropionate was used instead of ethyl bromoacetate. -Ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[564] In Example 14, the same mole of 3-octyloxy-4-hydroxy- in place of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 6- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used.
[565] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[566] 11.12 (bs, 1H), 9.96 (bs, 1H), 6.80-7.20 (m, 3H), 4.40 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H, J = 6.0 Hz), 3.21 (t , 2H, J = 5.0 Hz), 1.68 (m, 2H), 1.30-1.95 (m, 12H), 0.88 (t, 3H, J = 7.0 Hz)
[567] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[568] Elemental Analysis Value: as C ₂₀ H ₂₆ O ₇
[569] Calculated (%): C 63.48; H6.93; O29.60
[570] Found (%): C63.40; H6.88; O29.72
[571] Example 45 Synthesis of 3-hexyloxy-4-hydroxy-6- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound (194))
[572] In Reference Example 3, the same mole of 3-hexyloxy-4,6-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-hexyloxy-4-hydroxy-6- as in Reference Example 3, except that -1-benzopyran-2-one was used and ethyl 4-bromobutane was used instead of ethyl bromoacetate. (3-ethoxycarbonylpropyloxy) -2H-1-benzopyran-2-one was obtained.
[573] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -6- (3-ethoxycarbonylpropyloxy) -2H-1-benzopyran-2-one.
[574] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[575] 11.12 (bs, 1H), 9.98 (bs, 1H), 6.80-7.20 (m, 3H), 4.41 (t, 2H, J = 5.0 Hz), 3.99 (t, 2H, J = 6.0 Hz), 2.24 (t , 2H, J = 5.0Hz), 1.30-2.00 (m, 10H), 0.88 (t, 3H, J = 7.0Hz)
[576] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[577] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[578] Calculated (%): C 62.62; H6.64; O30.73
[579] Found (%): C 62.59; H6.75; O30.66
[580] Example 46 Synthesis of 3-hexyloxy-4-hydroxy-6- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (200))
[581] In Reference Example 3, the same mole of 3-hexyloxy-4,6-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-hexyloxy-4-hydroxy-6- was used in the same manner as in Reference Example 3 except that -1-benzopyran-2-one was used, and 5-bromopentane carbonate was used instead of ethyl bromoacetate. (5-ethoxycarbonylbutoxy) -2H-1-benzopyran-2-one was obtained.
[582] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -6- (5-ethoxycarbonylbutoxy) -2H-1-benzopyran-2-one.
[583] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[584] 11.15 (bs, 1H), 10.01 (bs, 1H), 6.80-7.20 (m, 3H), 4.40 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H, J = 6.0 Hz), 2.23 (t , 2H, J = 5.0 Hz), 1.30-2.00 (m, 12H), 0.88 (t, 3H, J = 7.0 Hz)
[585] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[586] Elemental Analysis Value: as C ₂₀ H ₂₆ O ₇
[587] Calculated (%): C 63.48; H6.93; O29.60
[588] Found (%): C 63.51; H6.81; O29.68
[589] Reference Example 6 Synthesis of 3-butoxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (207))]
[590] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-butoxy-4,7-dihydroxy-2H-1 3-butoxy-4-hydroxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used. Got it.
[591] In Example 1, the same mole of 3-butoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[592] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[593] 11.45 (bs, 1H), 7.72 (d, 1H, J = 7.2 Hz), 6.92 (s, 2H), 4.86 (bs, 1H), 4.07 (t, 2H, J = 6.8 Hz), 3.88 (t, 2H , J = 5.2 Hz, 3.78 (t, 2H, J = 5.2 Hz), 1.25-1.68 (m, 4H), 0.86 (t, 3H, J = 7.2 Hz)
[594] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[595] Elemental Analysis Value: As C ₁₅ H ₁₈ O ₆
[596] Calculated (%): C 61.21; H6.17; O32.62
[597] Found (%): C 61.38; H6.18; O32.44
[598] Reference Example 7 Synthesis of 3-hexyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (210))
[599] In Reference Example 1, the same mole of 3-hexyloxy-4,7-dihydroxy-2H- in place of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-hexyloxy-4-hydroxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2- in the same manner as in Reference Example 1 except that 1-benzopyran-2-one was used. Got on.
[600] In Example 1, the same mole of 3-butoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[601] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[602] 11.49 (bs, 1H), 7.71 (d, 1H, J = 7.2 Hz), 6.94 (s, 2H), 4.86 (bs, 1H), 4.07 (t, 2H, J = 6.8 Hz), 3.86 (t, 2H , J = 5.2 Hz), 3.74 (t, 2H, J = 5.2 Hz), 1.20-1.40 (m, 8H), 0.86 (t, 3H, J = 7.2 Hz)
[603] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[604] Elemental Analysis Value: As C ₁₇ H ₂₂ O ₆
[605] Calculated (%): C 63.34; H6.88; O29.79
[606] Found (%): C 63.39; H6.91; O29.70
[607] Reference Example 8 Synthesis of 3-octyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (216))
[608] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4,7-dihydroxy-2H-1 3-octyloxy-4-hydroxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used. Got it.
[609] In Example 1, instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4-hydroxy The title compound was obtained in the same manner as in Example 1 except that oxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[610] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[611] 11.50 (bs, 1H), 7.70 (d, 1H, J = 7.2 Hz), 6.95 (s, 2H), 4.91 (bs, 1H), 4.07 (t, 2H, J = 6.8 Hz), 3.88 (t, 2H , J = 5.2 Hz, 3.73 (t, 2H, J = 5.2 Hz), 1.68 (m, 2H), 1.25-1.40 (m, 10H), 0.86 (t, 3H, J = 7.2 Hz)
[612] IR (KBr, cm ^-1 ): 3300, 3005, 1660, 1610, 1230
[613] Elemental Analysis Value: as C ₁₉ H ₂₆ O ₆
[614] Calculated (%): C 65.12; H7.48; O27.40
[615] Found (%): C65.48; H7.18; O27.34
[616] Reference Example 9 Synthesis of 3-geranyloxy-4-hydroxy-7- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (226))
[617] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-geranyloxy-4,7-dihydroxy-2H- A 3-geranyloxy-4-hydroxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2- was carried out in the same manner as in Reference Example 1 except that 1-benzopyran-2-one was used. Got on.
[618] In Example 1, the same mole of 3-geranyloxy-4- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that hydroxy-7- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[619] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[620] 9.30 (bs, 1H), 7.74 (d, 1H, J = 7.2 Hz), 6.93 (s, 2H), 5.40 (m, 1H), 5.25 (m, 1H), 5.10 (m, 1H), 4.88 (bs , 1H), 4.21 (m, 2H), 4.05 (t, 2H, J = 6.0 Hz), 3.77 (t, 2H, J = 6.0 Hz), 3.77 (t, 2H, J = 6.0 Hz), 1.50-2.15 (m, 13 H)
[621] IR (KBr, cm ^-1 ): 3300, 3005, 1660, 1610, 1230
[622] Elemental Analysis Value: as C ₂₁ H ₂₆ O ₆
[623] Calculated (%): C 67.36; H7.00; O25.64
[624] Found (%): C67.40; H7.10; O25.50
[625] Reference Example 10 Synthesis of 3-octyloxy-4-hydroxy-7- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (249))
[626] In Reference Example 2, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4,7-dihydroxy-2H- 3-octyloxy-4-hydroxy-7- (2,2-dimethyl-1,3-dioxolane-4-methoxy) in the same manner as in Reference Example 2 except that 1-benzopyran-2-one was used. -2H-1-benzopyran-2-one was obtained.
[627] In Example 12, instead of 3-hexyloxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one , Except using the same mole 3-octyloxy-4-hydroxy-7- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one In the same manner as in Example 12, the title compound was obtained.
[628] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[629] 11.51 (bs, 1H), 7.70 (d, 1H, J = 8.2 Hz), 6.95 (m, 2H), 5.00 (s, 1H), 4.70 (s, 1H), 3.81-4.11 (m, 5H), 3.45 (s, 2H), 1.18-1.40 (m, 10H), 0.86 (t, 3H, J = 7.2 Hz)
[630] IR (KBr, cm ^-1 ): 3420, 3005, 1680, 1610, 1260
[631] Elemental Analysis Value: as C ₂₀ H ₂₈ O ₇
[632] Calculated (%): C 63.14; H7.42; O29.44
[633] Found (%): C63.38; H7.58; O29.04
[634] Reference Example 11 Synthesis of 3-hexyloxy-4-hydroxy-7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one
[635] In Reference Example 3, the same mole of 3-hexyloxy-4,7-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as the Reference Example 3 except that -1-benzopyran-2-one was used.
[636] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[637] 11.50 (bs, 1H), 7.72 (t, 1H, J = 7.0 Hz), 6.95 (s, 2H), 4.91 (s, 2H), 3.81-4.11 (m, 4H), 1.69 (m, 2H), 1.20 -1.40 (m, 9H), 0.88 (t, 3H, J = 7.0 Hz)
[638] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[639] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[640] Calculated (%): C 62.62; H6.64; O30.73
[641] Found (%): C 62.68; H6.58; O30.64
[642] Example 47 Synthesis of 3-hexyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (267))
[643] 3-hexyloxy-4-hydroxy-7- in Example 14 instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[644] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[645] 11.51 (bs, 1H), 11.10 (bs, 1H), 7.73 (t, 1H, J = 7.0 Hz), 6.94 (s, 2H), 4.88 (s, 2H), 3.89 (t, 2H, J = 5.0 Hz ), 1.69 (m, 2H), 1.20-1.40 (m, 6H), 0.86 (t, 3H, J = 7.0 Hz)
[646] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[647] Elemental Analysis Value: as C ₁₇ H ₂₀ O ₇
[648] Calculated (%): C 60.71; H5.99; O33.30
[649] Found (%): C 60.68; H6.07; O33.25
[650] Example 48 Synthesis of 3-ethoxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (261))
[651] In Reference Example 3, the same mole of 3-ethoxy-4,7-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one A 3-ethoxy-4-hydroxy-7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3, except that 1-benzopyran-2-one was used.
[652] In Example 14, the same mole of 3-ethoxy-4-hydroxy- instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using 7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one.
[653] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[654] 11.51 (bs, 1H), 11.14 (bs, 1H), 7.73 (t, 1H, J = 7.0 Hz), 6.95 (s, 2H), 4.86 (s, 2H), 4.08 (q, 2H, J = 6.0 Hz ), 1.26 (t, 3H, J = 7.0 Hz)
[655] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[656] Elemental Analysis Value: as C ₁₃ H ₁₂ O ₇
[657] Calculated (%): C 55.72; H4.32; O39.97
[658] Found (%): C55.68; H4.23; O40.09
[659] Example 49 Synthesis of 3-butoxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (264))
[660] In Reference Example 3, the same mole of 3-ethoxy-4,7-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one A 3-butoxy-4-hydroxy-7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used.
[661] In Example 14, the same mole of 3-butoxy-4-hydroxy- as an alternative to 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using 7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one.
[662] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[663] 11.49 (bs, 1H), 11.11 (bs, 1H), 7.72 (t, 1H, J = 7.0 Hz), 6.94 (s, 2H), 4.89 (s, 2H), 3.96 (t, 2H, J = 6.0 Hz ), 1.30 to 1.95 (m, 4H), 0.88 (t, 3H, J = 7.0 Hz)
[664] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[665] Elemental Analysis Value: as C ₁₅ H ₁₆ O ₇
[666] Calculated (%): C 58.44; H5.23; O36.33
[667] Found (%): C 58.51; H5.19; O36.30
[668] Example 50 Synthesis of 3-octyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (273))
[669] In Reference Example 3, the same mole of 3-octyloxy-4,7-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-octyloxy-4-hydroxy-7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used. .
[670] In Example 14, the same mole of 3-octyloxy-4-hydroxy- in place of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[671] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[672] 11.54 (bs, 1H), 11.14 (bs, 1H), 7.71 (t, 1H, J = 7.0 Hz), 6.94 (s, 2H), 4.87 (s, 2H), 3.98 (t, 2H, J = 6.0 Hz ), 1.30 to 1.95 (m, 12H), 0.86 (t, 3H, J = 7.0 Hz)
[673] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[674] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[675] Calculated (%): C 62.62; H6.64; O30.73
[676] Found (%): C 62.60; H6.73; O30.67
[677] Example 51 Synthesis of 3-geranyloxy-4-hydroxy-7-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (283))
[678] In Reference Example 3, the same mole of 3-geranyloxy-4,7-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-geranyloxy-4-hydroxy-7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one except that -1-benzopyran-2-one was used as in Reference Example 3 Got.
[679] In Example 14, the same mole of 3-geranyloxy-4-hydroxy instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -7-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one.
[680] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[681] 11.51 (bs, 1H), 11.10 (bs, 1H), 7.73 (t, 1H, J = 7.0 Hz), 6.95 (s, 2H), 5.39 (m, 1H), 5.24 (m, 1H), 5.10 (m , 1H), 4.87 (s, 2H), 4.25 (m, 2H), 4.05 (t, 2H, J = 6.0Hz), 3.79 (t, 2H, J = 6.0Hz), 1.50-2.15 (m, 13H)
[682] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[683] Elemental Analysis Value: as C ₂₁ H ₂₄ O ₇ .
[684] Calculated (%): C64.93; H6.23; O28.84
[685] Found (%): C65.01; H6.11; O28.88
[686] Example 52 Synthesis of 3-butoxy-4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (287))
[687] In Reference Example 3, the same mole of 3-butoxy-4,7-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one Except for using 1-benzopyran-2-one and using 3-bromopropionate instead of ethyl bromoacetate, 3-butoxy-4-hydroxy-7- ( 2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[688] In Example 14, the same mole of 3-butoxy-4-hydroxy- as an alternative to 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14, except that 7- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used.
[689] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[690] 11.54 (bs, 1H), 11.09 (bs, 1H), 7.72 (t, 1H, J = 7.0 Hz), 6.94 (s, 2H), 4.42 (t, 2H, J = 5.0 Hz), 3.97 (t, 2H , J = 6.0 Hz), 3.17 (t, 2H, J = 5.0 Hz), 1.30-1.95 (m, 4H), 0.88 (t, 3H, J = 7.0 Hz)
[691] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[692] Elemental Analysis Value: As C ₁₆ H ₁₈ O ₇
[693] Calculated (%): C 59.62; H5.63; O34.75
[694] Found (%): C59.67; H5.51; O34.82
[695] Example 53 Synthesis of 3-hexyloxy-4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (288))
[696] In Reference Example 3, the same mole of 3-hexyloxy-4,7-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-Hexyloxy-4-hydroxy-7 was used in the same manner as in Reference Example 3, except that -1-benzopyran-2-one was used and ethyl 3-bromopropionate was used instead of ethyl bromoacetate. -(2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[697] In Example 14, the same molar 3-hexyloxy-4-hydroxy instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -7- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one.
[698] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[699] 11.51 (bs, 1H), 11.12 (bs, 1H), 7.73 (t, 1H, J = 7.0 Hz), 6.94 (s, 2H), 4.46 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H , J = 6.0 Hz), 3.18 (t, 2H, J = 5.0 Hz), 1.69 (m, 2H), 1.30-1.95 (m, 8H), 0.88 (t, 3H, J = 7. 0 Hz)
[700] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[701] Elemental Analysis Value: as C ₁₈ H ₂₂ O ₇
[702] Calculated (%): C 61.70; H6.33; O31.97
[703] Found (%): C 61.65; H6.28; O32.07
[704] Example 54 Synthesis of 3-octyloxy-4-hydroxy-7- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (289))
[705] In Reference Example 3, the same mole of 3-octyloxy-4,7-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one Except for using 1-benzopyran-2-one and using 3-bromopropionate instead of ethyl bromoacetate, 3-octyloxy-4-hydroxy-7- ( 2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[706] In Example 14, the same mole of 3-octyloxy-4-hydroxy- in place of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except that 7- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used.
[707] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[708] 11.49 (bs, 1H), 11.10 (bs, 1H), 7.73 (t, 1H, J = 7.0 Hz), 6.94 (s, 2H), 4.40 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H , J = 6.0 Hz), 3.21 (t, 2H, J = 5.0 Hz), 1.68 (m, 2H), 1.30-1.95 (m, 12H), 0.88 (t, 3H, J = 7.0 Hz)
[709] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[710] Elemental Analysis Value: as C ₂₀ H ₂₆ O ₇
[711] Calculated (%): C 63.48; H6.93; O29.60
[712] Found (%): C 63.51; H6.97; O29.52
[713] Example 55 Synthesis of 3-hexyloxy-4-hydroxy-7- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound 295)
[714] In Reference Example 3, the same mole of 3-hexyloxy-4,7-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-hexyloxy-4-hydroxy-7 was used in the same manner as in Reference Example 3 except that -1-benzopyran-2-one was used and 3-bromobutyrate was used instead of ethyl bromoacetate. -(2-ethoxycarbonylpropyloxy) -2H-1-benzopyran-2-one was obtained.
[715] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -7- (2-ethoxycarbonylpropyloxy) -2H-1-benzopyran-2-one.
[716] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[717] 11.54 (bs, 1H), 11.12 (bs, 1H), 7.73 (t, 1H, J = 7.0 Hz), 6.92 (s, 2H), 4.41 (t, 2H, J = 5.0 Hz), 3.99 (t, 2H , J = 6.0 Hz), 2.24 (t, 2H, J = 5.0 Hz), 1.30-2.00 (m, 10H), 0.89 (t, 3H, J = 7.0 Hz)
[718] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[719] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[720] Calculated (%): C 62.62; H6.64; O30.73
[721] Found (%): C 62.52; H6.79; O30.69
[722] Example 56 Synthesis of 3-hexyloxy-4-hydroxy-7- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (301))
[723] In Reference Example 3, the same mole of 3-hexyloxy-4,7-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-hexyloxy-4-hydroxy-7- as in Reference Example 3, except that -1-benzopyran-2-one was used and ethyl 5-bromopentane carbonate was used instead of ethyl bromoacetate. (2-ethoxycarbonylbutoxy) -2H-1-benzopyran-2-one was obtained.
[724] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -7- (2-ethoxycarbonylbutoxy) -2H-1-benzopyran-2-one.
[725] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[726] 11.53 (bs, 1H), 11.12 (bs, 1H), 7.71 (t, 1H, J = 7.0 Hz), 6.94 (s, 2H), 4.40 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H , J = 6.0 Hz), 2.23 (t, 2H, J = 5.0 Hz), 1.30-2.00 (m, 12H), 0.88 (t, 3H, J = 7.0 Hz)
[727] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[728] Elemental Analysis Value: as C ₂₀ H ₂₆ O ₇
[729] Calculated (%): C 63.48; H6.93; O29.60
[730] Found (%): C 63.56; H6.82; O29.62
[731] Example 57 Synthesis of 3-ethoxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound 305)]
[732] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-ethoxy-4,8-dihydroxy-2H-1 3-Ethoxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used. Got it.
[733] In Example 1, the same mole of 3-ethoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[734] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[735] 10.39 (bs, 1H), 6.70 to 7.60 (m, 3H), 4.88 (bs, 1H), 4.16 (t, 2H, J = 5.0 Hz), 4.08 (q, 2H, J = 6.0 Hz), 3.77 (t , 2H, J = 5.0 Hz), 1.22 (t, 3H, J = 7.0 Hz)
[736] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[737] Elemental Analysis Value: As C ₁₃ H ₁₄ O ₆
[738] Calculated (%): C 58.64; H5.30; O36.06
[739] Found (%): C58.72; H5.19; O36.09
[740] Example 58 Synthesis of 3-butoxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (308))
[741] In Reference Example 1, the same mole of 3-butoxy-4,8-dihydroxy-2H-1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one A 3-butoxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used. Got it.
[742] In Example 1, the same mole of 3-butoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[743] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[744] 10.41 (bs, 1H), 6.70 to 7.60 (m, 3H), 4.82 (bs, 1H), 4.09 (t, 2H, J = 6.0 Hz), 3.82 (t, 2H, J = 5.0 Hz), 3.75 (t , 2H, J = 6.0Hz), 1.30-1.80 (m, 4H), 0.88 (t, 3H, J = 7.0Hz)
[745] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[746] Elemental Analysis Value: As C ₁₅ H ₁₈ O ₆
[747] Calculated (%): C 61.21; H6.17; O32.62
[748] Found (%): C 61.26; H6.09; O32.65
[749] Example 59 Synthesis of 3-hexyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound 311)
[750] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-hexyloxy-4,8-dihydroxy-2H- 3-hexyloxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2- in the same manner as in Reference Example 1 except that 1-benzopyran-2-one was used. Got on.
[751] In Example 1, the same mole of 3-hexyloxy-4- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[752] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[753] 10.43 (bs, 1H), 6.70 to 7.60 (m, 3H), 4.91 (bs, 1H), 4.03 (t, 2H, J = 6.0 Hz), 3.90 (t, 2H, J = 5.0 Hz), 3.76 (t , 2H, J = 6.0Hz), 1.30-1.80 (m, 8H), 0.87 (t, 3H, J = 7.0Hz)
[754] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[755] Elemental Analysis Value: As C ₁₇ H ₂₂ O ₆
[756] Calculated (%): C 63.34; H6.88; O29.79
[757] Found (%): C 63.39; H6.94; O29.67
[758] Example 60 Synthesis of [3- (4-Methylpentyloxy) -4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (315)) ]
[759] In Reference Example 1, the same mole of 3- (4-methylpentyloxy) -4,8-dihydro instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3- (4-methylpentyloxy) -4-hydroxy-8- (2-acetoxyethoxy) -2H as in Reference Example 1, except that oxy-2H-1-benzopyran-2-one was used. -1-benzopyran-2-one was obtained.
[760] Example 1, instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one, the same mole of 3- (4-methylpentyloxy The title compound was obtained in the same manner as in Example 1 except for using 4--4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one.
[761] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[762] 10.35 (bs, 1H), 6.70 to 7.60 (m, 3H), 4.83 (bs, 1H), 4.06 (t, 2H, J = 6.0 Hz), 3.84 (t, 2H, J = 5.0 Hz), 3.77 (t , 2H, J = 6.0Hz), 1.20-1.80 (m, 5H), 0.88 (d, 6H, J = 3.0Hz)
[763] IR (KBr, cm ^-1 ): 3300, 3000, 1660, 1600, 1230
[764] Elemental Analysis Value: As C ₁₇ H ₂₂ O ₆
[765] Calculated (%): C 63.34; H6.88; O29.79
[766] Found (%): C 63.27; H6.96; O29.77
[767] Example 61 Synthesis of 3-octyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (317))
[768] In Reference Example 1, the same mole of 3-octyloxy-4,8-dihydroxy-2H-1 in place of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one A 3-octyloxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was prepared in the same manner as in Reference Example 1 except that benzopyran-2-one was used. Got it.
[769] In Example 1, instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4-hydroxy The title compound was obtained in the same manner as in Example 1 except that oxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[770] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[771] 10.43 (bs, 1H), 6.70 to 7.60 (m, 3H), 4.87 (bs, 1H), 4.05 (t, 2H, J = 6.0 Hz), 3.89 (t, 2H, J = 5.0 Hz), 3.79 (t , 2H, J = 6.0Hz), 1.20-1.80 (m, 12H), 0.87 (t, 3H, J = 6.0Hz)
[772] IR (KBr, cm ^-1 ): 3300, 3005, 1660, 1610, 1230
[773] Elemental Analysis Value: as C ₁₉ H ₂₆ O ₆
[774] Calculated (%): C 65.12; H7.48; O27.40
[775] Found (%): C65.03; H7.51; O27.46
[776] Example 62 Synthesis of 3-geranyloxy-4-hydroxy-8- (2-hydroxyethoxy) -2H-1-benzopyran-2-one (Compound (327))
[777] In Reference Example 1, the same mole of 3-geranyloxy-4,8-dihydroxy-2H- in place of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one Except for using 1-benzopyran-2-one as in Reference Example 1, 3-geranyloxy-4-hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2- Got on.
[778] In Example 1, the same mole of 3-geranyloxy-4- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that hydroxy-8- (2-acetoxyethoxy) -2H-1-benzopyran-2-one was used.
[779] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[780] 10.40 (bs, 1H), 6.70 to 7.70 (m, 3H), 5.36 (m, 1H), 5.27 (m, 1H), 5.09 (m, 1H), 4.86 (bs, 1H), 4.23 (m, 2H) , 4.04 (t, 2H, J = 6.0 Hz), 3.76 (t, 2H, J = 6.0 Hz), 1.50-2.15 (m, 13H)
[781] IR (KBr, cm ^-1 ): 3300, 3005, 1660, 1610, 1230
[782] Elemental Analysis Value: as C ₂₁ H ₂₆ O ₆
[783] Calculated (%): C 67.36; H7.00; O25.64
[784] Found (%): C67.30; H7.11; O25.59
[785] Example 63 Synthesis of 3-butoxy-4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (331))
[786] In Reference Example 1, the same mole of 3-butoxy-4,8-dihydroxy-2H-1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-ethoxy-4-hydroxy-8- was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. (3-acetoxypropyloxy) -2H-1-benzopyran-2-one was obtained.
[787] In Example 1, the same mole of 3-ethoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-8- (3-acetoxypropyloxy) -2H-1-benzopyran-2-one was used.
[788] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[789] 10.39 (bs, 1H), 6.70 to 7.60 (m, 3H), 4.88 (bs, 1H), 3.90 to 4.00 (m, 4H), 3.72 (t, 2H, J = 6.0 Hz), 1.30 to 1.95 (m, 6H), 0.89 (t, 3H, J = 7.0 Hz)
[790] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[791] Elemental Analysis Value: As C ₁₆ H ₂₀ O ₆
[792] Calculated (%): C 62.32; H6.54; O31.14
[793] Found (%): C 62.40; H6.57; O31.03
[794] Example 64 Synthesis of 3-hexyloxy-4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (332))
[795] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-hexyloxy-4,8-dihydroxy-2H- 3-hexyloxy-4-hydroxy- as in Reference Example 1, except that 1-benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. 8- (3-acetoxypropyloxy) -2H-1-benzopyran-2-one was obtained.
[796] In Example 1, the same mole of 3-hexyloxy-4- in place of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that hydroxy-8- (3-acetoxypropyloxy) -2H-1-benzopyran-2-one was used.
[797] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[798] 10.43 (bs, 1H), 6.70 to 7.60 (m, 3H), 4.87 (bs, 1H), 3.90 to 4.00 (m, 4H), 3.72 (t, 2H, J = 6.0 Hz), 1.20 to 1.95 (m, 10H), 0.87 (t, 3H, J = 7.0 Hz)
[799] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[800] Elemental Analysis Value: as C ₁₈ H ₂₄ O ₆
[801] Calculated (%): C64.27; H7.19; O28.54
[802] Found (%): C64.23; H7.14; O28.63
[803] Example 65 Synthesis of 3-octyloxy-4-hydroxy-8- (3-hydroxypropyloxy) -2H-1-benzopyran-2-one (Compound 334)]
[804] In Reference Example 1, the same mole of 3-octyloxy-4,8-dihydroxy-2H-1 in place of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-octyloxy-4-hydroxy-8- was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 3-bromopropyl acetate was used instead of 2-bromoethyl acetate. (3-acetoxypropyloxy) -2H-1-benzopyran-2-one was obtained.
[805] In Example 1, instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one, the same mole of 3-octyloxy-4-hydroxy The title compound was obtained in the same manner as in Example 1 except that oxy-8- (3-acetoxypropyloxy) -2H-1-benzopyran-2-one was used.
[806] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[807] 10.37 (bs, 1H), 6.70 to 7.60 (m, 3H), 4.89 (bs, 1H), 3.90 to 4.00 (m, 4H), 3.70 (t, 2H, J = 6.0 Hz), 1.20 to 1.95 (m, 14H), 0.86 (t, 3H, J = 7.0 Hz)
[808] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[809] Elemental Analysis Value: As C ₂₀ H ₂₈ O ₆
[810] Calculated (%): C 65.91; H7.74; O26.34
[811] Found (%): C65.96; H7.79; O26.25
[812] Example 66 Synthesis of 3-ethoxy-4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (339))
[813] In Reference Example 1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-ethoxy-4,8-dihydroxy-2H-1 3-Ethoxy-4-hydroxy-8- was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 4-bromobutyl acetate was used instead of 2-bromoethyl acetate. (4-acetoxybutoxy) -2H-1-benzopyran-2-one was obtained.
[814] In Example 1, the same mole of 3-ethoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-8- (4-acetoxybutoxy) -2H-1-benzopyran-2-one was used.
[815] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[816] 10.43 (bs, 1H), 6.70 to 7.60 (m, 3H), 4.81 (bs, 1H), 4.19 (t, 2H, J = 5.0 Hz), 3.95 (q, 2H, J = 6.0 Hz), 3.78 (t , 2H, J = 5.0Hz), 1.40-1.75 (m, 4H), 1.22 (t, 3H, J = 7.0Hz)
[817] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[818] Elemental Analysis Value: As C ₁₅ H ₁₈ O ₆
[819] Calculated (%): C 61.21; H6.17; O32.62
[820] Found (%): C 61.32; H6.13; O32.55
[821] Example 67 Synthesis of 3-butoxy-4-hydroxy-8- (4-hydroxybutoxy) -2H-1-benzopyran-2-one (Compound (340))]
[822] In Reference Example 1, the same mole of 3-butoxy-4,8-dihydroxy-2H-1, instead of 3-ethoxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-Butoxy-4-hydroxy-8- was used in the same manner as in Reference Example 1 except that benzopyran-2-one was used and 4-bromobutyl acetate was used instead of 2-bromoethyl acetate. (4-acetoxybutoxy) -2H-1-benzopyran-2-one was obtained.
[823] In Example 1, the same mole of 3-butoxy-4-hydroxy instead of 3-ethoxy-4-hydroxy-5- (2-acetoxyethoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 1 except that oxy-8- (4-acetoxybutoxy) -2H-1-benzopyran-2-one was used.
[824] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[825] 10.32 (bs, 1H), 6.70 to 7.60 (m, 3H), 4.86 (bs, 1H), 3.90 to 4.00 (m, 4H), 3.74 (t, 2H, J = 6.0 Hz), 1.30 to 1.95 (m, 8H), 0.88 (t, 3H, J = 7.0 Hz)
[826] IR (KBr, cm ^-1 ): 3300, 3005, 1670, 1600, 1230
[827] Elemental Analysis Value: As C ₁₇ H ₂₂ O ₆
[828] Calculated (%): C 63.34; H6.88; O29.78
[829] Found (%): C 63.28; H6.97; O29.75
[830] Reference Example 12 [3-hexyloxy-4-hydroxy-8- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one synthesis]
[831] In Reference Example 2, 3-hexyloxy-4,8-dihydroxy-2H-1-instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one A title compound was obtained in the same manner as in Reference Example 2 except that benzopyran-2-one was used.
[832] ¹ H-NMR (CDCl ₃ , δ-TMS):
[833] 10.45 (bs, 1H), 6.70 to 7.50 (m, 3H), 4.50 (t, 2H, J = 5.2 Hz), 3.90 to 4.21 (m, 5H), 1.72 (m, 2H), 1.48 (s, 3H) , 1.42 (s, 3H), 1.20-1.41 (m, 6H), 0.86 (t, 3H, J = 7.0 Hz)
[834] IR (KBr, cm ^-1 ): 3300, 3005, 1725, 1600, 1230
[835] Elemental Analysis Value: As C ₂₁ H ₂₈ O ₇ .
[836] Calculated (%): C64.27; H7.19; O28.54
[837] Found (%): C64.21; H7.31; O28.48
[838] Example 68 Synthesis of 3-hexyloxy-4-hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (349))
[839] In Example 12, instead of 3-hexyloxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one , 3-hexyloxy-4-hydroxy-8- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2 of the same mole obtained in Reference Example 12 A title compound was obtained in the same manner as in Example 12, except that -on was used.
[840] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[841] 10.43 (bs, 1H), 6.70 to 7.50 (m, 3H), 4.95 (s, 1H), 4.69 (s, 1H), 3.81 to 4.11 (m, 5H), 3.43 (s, 2H), 1.70 (m, 2H), 1.18-1.40 (m, 6H), 0.88 (t, 3H, J = 7.0 Hz)
[842] IR (KBr, cm ^-1 ): 3420, 3005, 1680, 1610, 1260
[843] Elemental Analysis Value: as C ₁₈ H ₂₄ O ₇
[844] Calculated (%): C 61.35; H6.86; O31.78
[845] Found (%): C 61.26; H6.99; O31.75
[846] Example 69 Synthesis of 3-butoxy-4-hydroxy-8- (2,3-dihydroxypropyloxy) -2H-1-benzopyran-2-one (Compound (348))
[847] In the Reference Example 2, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one, the same mole of 3-butoxy-4,8-dihydroxy-2H- Except for using 1-benzopyran-2-one as in Reference Example 2, 3-butoxy-4-hydroxy-8- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one was obtained.
[848] In Example 12, instead of 3-hexyloxy-4-hydroxy-5- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one , Except using the same mole 3-butoxy-4-hydroxy-8- (2,2-dimethyl-1,3-dioxolane-4-methoxy) -2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 12.
[849] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[850] 10.37 (bs, 1H), 6.70 to 7.60 (m, 3H), 5.04 (s, 1H), 4.70 (s, 1H), 3.81 to 4.11 (m, 5H), 3.44 (s, 2H), 1.18 to 1.40 ( m, 4H), 0.89 (t, 3H, J = 7.0 Hz)
[851] IR (KBr, cm ^-1 ): 3420, 3005, 1680, 1610, 1260
[852] Elemental Analysis Value: as C ₁₆ H ₂₀ O ₇
[853] Calculated (%): C 59.25; H6.22; O34.53
[854] Found (%): C59.22; H6.36; O34.42
[855] Reference Example 13 Synthesis of 3-hexyloxy-4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one
[856] In Reference Example 3, 3-hexyloxy-4,8-dihydroxy-2H-1-instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one A title compound was obtained in the same manner as in Reference Example 3 except that benzopyran-2-one was used.
[857] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[858] 10.41 (bs, 1H), 6.70 to 7.50 (m, 3H), 4.90 (s, 2H), 3.81 to 4.11 (m, 4H), 1.69 (m, 2H), 1.20 to 1.40 (m, 9H), 0.87 ( t, 3H, J = 7.0 Hz)
[859] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[860] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[861] Calculated (%): C 62.62; H6.64; O30.73
[862] Found (%): C 62.54; H6.59: O30.87
[863] Example 70 Synthesis of 3-hexyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (368))
[864] In Example 14, the same mole of 3-hexyloxy as obtained in Reference Example 13, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14, except that 4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[865] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[866] 11.12 (bs, 1H), 10.40 (bs, 1H), 6.80 to 7.70 (m, 3H), 4.86 (s, 2H), 3.89 (t, 2H, J = 5.0 Hz), 1.69 (m, 2H), 1.20 -1.40 (m, 6H), 0.88 (t, 3H, J = 7.0 Hz)
[867] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[868] Elemental Analysis Value: as C ₁₇ H ₂₀ O ₇
[869] Calculated (%): C 60.71; H5.99; O33.30
[870] Found (%): C 60.69; H6.07; O33.24
[871] Example 71 Synthesis of 3-ethoxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (362))
[872] For Reference Example 3, the same mole of 3-ethoxy-4,8-di as obtained in Reference Example 13 instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one Except for using hydroxy-2H-1-benzopyran-2-one, in the same manner as in Reference Example 3 3-ethoxy-4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2 -Got on.
[873] In Example 14, the same mole of 3-ethoxy-4-hydroxy- instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14, except that 8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[874] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[875] 11.14 (bs, 1H), 10.36 (bs, 1H), 6.80-7.70 (m, 3H), 4.86 (s, 2H), 4.08 (q, 2H, J = 6.0 Hz), 1.27 (t, 3H, J = 7.0 Hz)
[876] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[877] Elemental Analysis Value: as C ₁₃ H ₁₂ O ₇
[878] Calculated (%): C 55.72; H4.32; O39.97
[879] Found (%): C55.67; H4.28; O40.05
[880] Example 72 Synthesis of 3-butoxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (365))
[881] In Reference Example 3, the same mole of 3-butoxy-4,8-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one A 3-butoxy-4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used.
[882] In Example 14, the same mole of 3-butoxy-4-hydroxy- as an alternative to 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14, except that 8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[883] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[884] 11.14 (bs, 1H), 10.37 (bs, 1H), 6.80-7.70 (m, 3H), 4.86 (s, 2H), 3.98 (t, 2H, J = 6.0 Hz), 1.30-1.95 (m, 4H) , 0.87 (t, 3H, J = 7.0 Hz)
[885] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[886] Elemental Analysis Value: as C ₁₅ H ₁₆ O ₇
[887] Calculated (%): C 58.44; H5.23; O36.33
[888] Found (%): C58.50; H5.11; O36.39
[889] Example 73 Synthesis of 3-octyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (374))
[890] In Reference Example 3, the same mole of 3-octyloxy-4,8-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one A 3-octyloxy-4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3 except that 1-benzopyran-2-one was used. .
[891] In Example 14, the same mole of 3-octyloxy-4-hydroxy- in place of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14, except that 8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was used.
[892] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[893] 11.16 (bs, 1H), 10.41 (bs, 1H), 6.80-7.70 (m, 3H), 4.89 (s, 2H), 3.95 (t, 2H, J = 6.0 Hz), 1.30-1.95 (m, 12H) , 0.87 (t, 3H, J = 7.0 Hz)
[894] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[895] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[896] Calculated (%): C 62.62; H6.64; O30.73
[897] Found (%): C 62.67; H6.71; O30.62
[898] Example 74 Synthesis of 3-geranyloxy-4-hydroxy-8-hydroxycarbonylmethoxy-2H-1-benzopyran-2-one (Compound (384))
[899] In Reference Example 3, the same mole of 3-geranyloxy-4,8-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-octyloxy-4-hydroxy-8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one was obtained in the same manner as in Reference Example 3, except that -1-benzopyran-2-one was used. .
[900] In Example 14, the same mole of 3-geranyloxy-4-hydroxy instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -8-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one.
[901] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[902] 11.19 (bs, 1H), 10.36 (bs, 1H), 6.80 to 7.70 (m, 3H), 5.39 (m, 1H), 5.24 (m, 1H), 5.10 (m, 1H), 4.87 (s, 2H) , 4.25 (m, 2H), 4.05 (t, 2H, J = 6.0 Hz), 3.79 (t, 2H, J = 6.0 Hz), 1.50-2.15 (m, 13H)
[903] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[904] Elemental Analysis Value: as C ₂₁ H ₂₄ O ₇ .
[905] Calculated (%): C64.93; H6.23; O28.84
[906] Found (%): C64.87; H6.34; O28.79
[907] Example 75 Synthesis of 3-butoxy-4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (388))
[908] In Reference Example 3, the same mole of 3-butoxy-4,8-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one Except for using 1-benzopyran-2-one and using 3-bromopropionate instead of ethyl bromoacetate, 3-butoxy-4-hydroxy-8- ( 2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[909] In Example 14, the same mole of 3-butoxy-4-hydroxy- as an alternative to 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14, except that 8- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used.
[910] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[911] 11.19 (bs, 1H), 10.39 (bs, 1H), 6.80-7.70 (m, 3H), 4.42 (t, 2H, J = 5.0 Hz), 3.98 (t, 2H, J = 6.0 Hz), 3.17 (t , 2H, J = 5.0 Hz), 1.30-1.95 (m, 4H), 0.87 (t, 3H, J = 7. 0 Hz)
[912] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[913] Elemental Analysis Value: As C ₁₆ H ₁₈ O ₇
[914] Calculated (%): C 59.62; H5.63; O34.75
[915] Found (%): C59.69; H5.44; O34.87
[916] Example 76 Synthesis of 3-hexyloxy-4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (389))
[917] In Reference Example 3, the same mole of 3-hexyloxy-4,8-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-Hexyloxy-4-hydroxy-8 as in Reference Example 3, except that -1-benzopyran-2-one was used and 3-bromopropionate was used instead of ethyl bromoacetate. -(2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[918] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -8- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one.
[919] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[920] 11.12 (bs, 1H), 10.38 (bs, 1H), 6.80-7.70 (m, 3H), 4.46 (t, 2H, J = 5.0 Hz), 3.99 (t, 2H, J = 6.0 Hz), 3.20 (t , 2H, J = 5.0 Hz), 1.69 (m, 2H), 1.30-1.95 (m, 8H), 0.88 (t, 3H, J = 7.0 Hz)
[921] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[922] Elemental Analysis Value: as C ₁₈ H ₂₂ O ₇
[923] Calculated (%): C 61.70; H6.33; O31.97
[924] Found (%): C 61.64; H6.47; O31.89
[925] Example 77 Synthesis of 3-octyloxy-4-hydroxy-8- (2-hydroxycarbonylethoxy) -2H-1-benzopyran-2-one (Compound (390))
[926] In Reference Example 3, the same mole of 3-octyloxy-4,8-dihydroxy-2H- in place of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one Except for using 1-benzopyran-2-one and using 3-bromopropionate instead of ethyl bromoacetate, 3-octyloxy-4-hydroxy-8- ( 2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was obtained.
[927] In Example 14, the same mole of 3-octyloxy-4-hydroxy- in place of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14, except that 8- (2-ethoxycarbonylethoxy) -2H-1-benzopyran-2-one was used.
[928] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[929] 11.14 (bs, 1H), 10.36 (bs, 1H), 6.80-7.70 (m, 3H), 4.41 (t, 2H, J = 5.0 Hz), 3.97 (t, 2H, J = 6.0 Hz), 3.20 (t , 2H, J = 5.0 Hz), 1.68 (m, 2H), 1.30-1.95 (m, 12H), 0.88 (t, 3H, J = 7.0 Hz)
[930] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[931] Elemental Analysis Value: as C ₂₀ H ₂₆ O ₇
[932] Calculated (%): C 63.48; H6.93; O29.60
[933] Found (%): C63.53; H6.81; O29.66
[934] Example 78 Synthesis of 3-hexyloxy-4-hydroxy-8- (3-hydroxycarbonylpropyloxy) -2H-1-benzopyran-2-one (Compound (396))
[935] In Reference Example 3, the same mole of 3-hexyloxy-4,8-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-hexyloxy-4-hydroxy-8 as in Reference Example 3, except that -1-benzopyran-2-one was used and 3-bromobutane carbonate was used instead of ethyl bromoacetate. -(3-ethoxycarbonylpropyloxy) -2H-1-benzopyran-2-one was obtained.
[936] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -8- (3-ethoxycarbonylpropyloxy) -2H-1-benzopyran-2-one.
[937] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[938] 11.17 (bs, 1H), 10.44 (bs, 1H), 6.80-7.70 (m, 3H), 4.41 (t, 2H, J = 5.0 Hz), 3.99 (t, 2H, J = 6.0 Hz), 2.27 (t , 2H, J = 5.0Hz), 1.30-2.00 (m, 10H), 0.88 (t, 3H, J = 7.0Hz)
[939] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[940] Elemental Analysis Value: as C ₁₉ H ₂₄ O ₇ .
[941] Calculated (%): C 62.62; H6.64; O30.73
[942] Found (%): C 62.64; H6.51; O30.85
[943] Example 79 Synthesis of 3-hexyloxy-4-hydroxy-8- (4-hydroxycarbonylbutoxy) -2H-1-benzopyran-2-one (Compound (402))
[944] In Reference Example 3, the same mole of 3-hexyloxy-4,8-dihydroxy-2H, instead of 3-hexyloxy-4,5-dihydroxy-2H-1-benzopyran-2-one 3-hexyloxy-4-hydroxy-8 as in Reference Example 3, except that -1-benzopyran-2-one was used and 3-bromopentane carbonate was used instead of ethyl bromoacetate. -(4-ethoxycarbonylbutoxy) -2H-1-benzopyran-2-one was obtained.
[945] In Example 14, the same mole of 3-hexyloxy-4-hydroxy, instead of 3-hexyloxy-4-hydroxy-5-ethoxycarbonylmethoxy-2H-1-benzopyran-2-one The title compound was obtained in the same manner as in Example 14 except for using -8- (4-ethoxycarbonylbutoxy) -2H-1-benzopyran-2-one.
[946] ¹ H-NMR (DMSO-d ₆ , δ-TMS):
[947] 11.19 (bs, 1H), 10.47 (bs, 1H), 6.80-7.70 (m, 3H), 4.41 (t, 2H, J = 5.0 Hz), 3.99 (t, 2H, J = 6.0 Hz), 2.23 (t , 2H, J = 5.0 Hz), 1.30-2.00 (m, 12H), 0.86 (t, 3H, J = 7.0 Hz)
[948] IR (KBr, cm ^-1 ): 3420, 3005, 1750, 1610, 1260
[949] Elemental Analysis Value: as C ₂₀ H ₂₆ O ₇
[950] Calculated (%): C 63.48; H6.93; O29.60
[951] Found (%): C 63.45; H7.03; O29.52
[952] Example 80 Mouse Acute Toxicity Test
[953] Mice (ICR males, body weight 20-25 g, 5 groups 1) were added to each of 1000 and 2000 mg / kg of the compounds (1) to (404) with 0.5% methylcellulose suspension using gastric sonde. Forced oral administration.
[954] After administration, the animals were reared in the cage for 7 days, and the presence and death of the deceased animals were observed, and the 50% lethal dose (LD50: mg / kg) was estimated from the survival rate of the mice at the end of the observation. As a result, LD50 of the compounds (1)-(404) was 1000 mg / kg or more, and it turned out that the benzopyran derivative represented by the said general formula (I) is very safe.
[955] Example 81 Anti-allergic Test by Antigen-Induced Immediate and Delayed Airway Responses
[956] Test Methods:
[957] Male heartray morphots, 6 weeks old, were actively sensitized by inhaling 1% by mass of egg white albumin physiological saline solution for 10 minutes a day for 8 consecutive days using an ultrasonic nebulizer (NE-U12, Omron Corporation). One week after the final sensitization, 2 mass% egg white albumin physiological saline solution was inhaled for 5 minutes to cause asthma. Metyrapone (10 mg / kg) was injected intravenously 24 hours before and 1 hour before induction to inhibit endogenous steroid synthesis, and pyrilamine 30 minutes before induction of asthma to inhibit anaphylactic shock. (10 mg / kg) was administered intraperitoneally.
[958] After induction of asthma reaction, using airway resistance measuring device (Pulmos-I, MIPS Co., Ltd.), before induction of asthma, 1 minute after induction, 2 hours, 4 hours, 5 hours, 6 hours, 7 hours and 8 hours In addition, specific airway resistance's Raw was measured for 23 to 24 hours for 1 minute each. The airway resistance was calculated as the average value, and the airway resistance increase rate with respect to the airway resistance value before induction was calculated by the following equation.
[959] 10 mg / kg of the test substance shown in Table 1 was suspended in 0.5% aqueous solution of methyl cellulose, and administered orally once 1 hour before the induction of asthma reaction. Positive subjects (prednisolone) were orally administered 10 mg / kg 2 times 16 hours before and 2 hours before asthma reaction. In addition, animals were tested at 8 animals per group.
[960] According to this experimental method, an increase in airway resistance of two phases was observed immediately after inducing asthma and 4 to 8 hours after inducing asthma. In the present invention, the initial increase in airway resistance is referred to as immediate type asthma reaction, and the subsequent increase in airway resistance is referred to as delayed type asthma reaction. The evaluation of the drug refers to an asthma reaction-induced medium administration group (the group which does not administer the test drug after inducing an asthma reaction) according to the following equation 2, with an increase in the airway resistance increase rate 1 minute after the induction for the immediate asthma reaction. In the following, the inhibition rate for the "media administration group" is obtained. The results are shown collectively in Table 1.
[961] As for the late asthmatic reaction, the inhibition rate for the medium-administered group was determined according to the following Equation 3 by using the area under the time curve (AUC _4-8 ) of the increase rate of airway resistance from 4 to 8 hours after the induction of asthma reaction. The results are shown collectively in Table 1. As an example in FIG. 1, the relationship between the airway resistance increase rate and the time between 4-8 hours of inducing asthma reaction between the medium administration group, the positive control prednisolone administration group, and the compound 216 administration group is shown. Here, it is the area under the relationship between airway resistance growth rate and time (AUC _4-8 ).
[962] (Equation 1)
[963] Increase in airway resistance (%) = (Airway resistance after induction of asthma-Airway resistance before induction of asthma) ÷ Airway resistance before induction of asthma
[964] (Equation 2)
[965] Inhibition rate (%) = (Increased airway resistance rate 1 minute after induction of asthma reaction in the 1-substance-treated group ÷ increase rate of airway resistance 1 minute after induction of asthma in the medium-administered group) × 100
[966] (Equation 3)
[967] % Inhibition = (1 - AUC _4-8 ÷ causing the medium administration group of piheom substance group 1 minutes after the AUC _4-8) × 100
[968] As the comparative compound, the following six compounds and prednisolone were used.
[969] Comparative Compound (1): 3,4-Dihydroxy-7-methoxy-2H-1-benzopyran-2-one as described in Example 28 of WO 92/13852
[970] Comparative Compound (2): 3-methoxy-4-hydroxy-7-decyloxy-2H-1-benzopyran-2-one as described in Example 62 of WO 92/13852
[971] Comparative Compound (3): 3-hydroxy-4-butoxy-8-decyloxy-2H-1-benzopyran-2-one of Example 148 of WO 92/13852
[972] Comparative Compound (4): 7-methoxy-4-hydroxy-3- (β-D-glucopyronosyloxy) -based in Example 3 of Japanese Patent Laid-Open No. 7-145189 (US Pat. No. 55,255,953) 2H-1-benzopyran-2-one
[973] Comparative Compound (5): 7-butoxy-3-hydroxy-4- (β-D-glucopyro) as described in Example 6 of Japanese Patent Application Laid-Open No. 7-145190 (Example 61 in the specification of US Pat. No. 55,255,953). Nosyloxy) -2H-1-benzopyran-2-one
[974] Comparative Compound (6): 3-hydroxy-4-hexyloxy-7- (β-D-glucopyronosyloxy) as described in Example 19 of Japanese Patent Application Laid-Open No. 8-198890 (spec. US Patent No. 5580552). -2H-1-benzopyran-2-one
[975] Table 1
[976] Compound number% Inhibition of immediate form% Inhibition against late type Compound (8)14.158.2 Compound (14)32.465.5 Compound (29)15.860.9 Compound (53)19.359.8 Compound (65)21.560.2 Compound (81)15.454.1 Compound (99)14.661.9 Compound (109)14.066.8 Compound (115)31.861.7 Compound (137)8.358.9 Compound (147)19.159.5 Compound (166)23.564.1 Compound (202)19.957.8 Compound (207)8.571.7 Compound (210)14.271.4 Compound (216)38.872.5 Compound (226)22.861.5 Compound (249)28.863.4 Compound (267)14.062.2 Compound (273)32.964.5 Compound (288)13.459.1 Compound (311)11.955.4 Compound (349)12.557.2 Compound (368)24.860.0 Compound (390)29.761.1 Comparative Compound (1)5.721.9 Comparative Compound (2)6.520.2 Comparative Compound (3)5.224.3 Comparative Compound (4)4.720.5 Comparative Compound (5)6.822.4 Comparative Compound (6)5.924.1 Prednisolone29.051.4
[977] As is evident from the results shown in Table 1, the benzopyran derivatives represented by the general formula (I) exhibited an inhibitory effect of 8.3 to 38.8% against immediate asthma reactions, and also 54.1 to delayed asthma reactions. 72.5% showed a strong inhibitory effect. This inhibitory effect was stronger than that of the benzopyran derivatives previously reported by the present inventors tested with the comparative compound, and was at least equivalent to that of the prednisolone, a steroidal agent for the positive subject. From the above, it is clear that the benzopyran derivatives represented by the general formula (I) exhibit excellent therapeutic effects against allergic diseases such as asthma and are useful as anti-allergic agents.
[978] Below, the formulation example of the antiallergic agent which uses the benzopyran derivative represented by the said General formula (I) as an active ingredient is shown.
[979] Example 82 [5% Powdered Medicine]
[980] 50 mg of the compound (8) was ground with a mortar, 950 mg of lactose was added thereto, and mixed sufficiently while milling with a pestle to obtain a powdered medicine containing 5% by mass of the compound (8) of the present invention.
[981] Instead of the compound (8), the compound (14), (29), (53), (109), (137), (147), (166), (207), (210), (216), ( 249), (273) and (349) except having used each of the powdered medicine containing 5 mass% of said compounds as above was obtained.
[982] Example 83 10% Powdered Medicine
[983] 100 mg of the compound (8) was ground with a mortar, 900 mg of lactose was added thereto, and the mixture was sufficiently mixed while grinding with a pestle to obtain a powdered medicine containing 10% by mass of the compound (8).
[984] Instead of compound (8), compound (14), (29), (53), (109), (137), (147), (166), (207), (210), (216), ( A powdered medicine containing 10% by mass of each of the above-mentioned compounds was obtained in the same manner as above except that each of 249), (273) and (349) was used.
[985] Example 84 10% Granules
[986] The above compound (300 mg of 8 and 300 mg of starch were mixed and ground in a mortar. To this, 2000 mg of lactose and 370 mg of starch were added and mixed. Separately, 1 ml of purified water was added to 30 mg of gelatin, and dissolved by heating. 1 ml of ethanol was added to the mixture after cooling, the mixture was prepared into a gelatin solution, and the gelatin solution was added to the mixture prepared first, granulated, dried, stipulated, and contained 10% by mass of the compound (8). A granule was obtained.
[987] Instead of the compound (8), each of the compounds as described above, except that each of the compounds (14), (109), (115), (207), (210), (216) and (311) was used. The granules containing 10 mass% were obtained.
[988] Example 85 5 mg tablets
[989] 100 mg of the compound (8) is ground and mixed with 1240 mg of lactose and 400 mg of starch. 2000 mg of 10% starch paste is added to the formulation and mixed to assemble. After drying, 40 mg of talc and 20 mg of magnesium stearate were mixed and tableted at a ratio of 100 mg / tablet by a conventional method to obtain a tablet containing 5 mg of the compound (8).
[990] Instead of the compound (8), except that each of the compounds (14), (109), (115), (207), (210), (216), (267), (273) and (311) was used. As described above, a tablet containing 5 mg of the compound was obtained.
[991] Example 86 20 mg tablets
[992] 6 g of hydroxypropyl cellulose was dissolved in an appropriate amount of ethanol, and 94 g of lactose was added thereto and mixed. After drying slightly, it was sized with No. 60 sieve to obtain 6% hydroxypropyl cellulose lactose. In addition, magnesium stearate and talc were mixed in the ratio of 1: 4, and it was made into the stearic acid talc. 200 mg of the compound (8), 750 mg of 6% hydroxypropyl cellulose lactose, 20 mg of stearic acid talc, and 30 mg of varaisos starch were mixed well, and tableted at a ratio of 100 mg / tablet according to a conventional method. A tablet containing 20 mg of 8) was obtained.
[993] Instead of the compound (8), except that each of the compounds (14), (109), (115), (207), (210), (216), (267), (273) and (311) was used. As described above, a tablet containing 20 mg of the compound was obtained.
[994] Example 87 25 mg tablets
[995] 250 mg of the compound (8) was ground in a mortar and mixed well while adding 1220 mg of lactose to it. Appropriate amount of purified water was added to 500 mg of carboxymethyl starch, and the mixture was added and mixed for granulation. After drying, 20 mg of talc and 10 mg of magnesium stearate were mixed and tableted at a ratio of 200 mg / tablet according to a conventional method to obtain a tablet containing 25 mg of the compound (8).
[996] As described above, except that the compounds (14), (115), (208), (210), (216), (267), (311) and (349) were used instead of the compound (8). To obtain a tablet containing 25 mg of the compound.
[997] Example 88 10 mg Capsules
[998] 300 mg of the compound (8), 2000 mg of lactose, 670 mg of starch and 30 mg of gelatin were prepared as granules in the same manner as in Example 84, and then filled into No. 4 capsules at a ratio of 100 mg / capsule, thereby obtaining the compound (8). A capsule containing 10 mg was obtained.
[999] Instead of the compound (8), except for using each of the compound (14), (109), (115), (208), (210), (216), (267), (311) and (349) As described above, a capsule containing 10 mg of the compound was obtained.
[1000] Example 89 0.5% Ointment
[1001] 5 mg of the compound (208) and a small amount of liquid paraffin were ground to a dispersion, and separately prepared by heating and mixing liquid paraffin in an amount of 80 mg in total with 915 mg of white petrolatum and the first used liquid paraffin. The ointment containing 0.5 mass% of said compounds (208) was obtained by gradually adding the dispersion liquid prepared first, mixing well, and mixing it uniformly.
[1002] An ointment containing 0.5% by mass of the compound was obtained in the same manner as above except that the compound (210), (216), (267), (311) and (349) was used instead of the compound (208). .
[1003] The anti-allergic agent having the benzopyran derivative represented by the general formula (I) of the present invention or its physiologically acceptable salt as an active ingredient has high safety in terms of toxicity, and many of the benzopyran derivatives reported by the present inventors. It has a stronger anti-allergic action, and particularly shows an excellent therapeutic effect against immediate and delayed allergic diseases such as asthma.
[1004] Moreover, the benzopyran derivative represented by general formula (II) of this invention has high safety in terms of toxicity, and is useful as a medicine, especially an antiallergic agent.

权利要求:
Claims (19)
[1" claim-type="Currently amended] An antiallergic agent characterized in that the benzopyran derivative represented by the general formula (I) or a physiologically acceptable salt thereof as an active ingredient:

(Wherein R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms, and any one of R ² , R ³ , R ⁴ and R ⁵ is an alkoxyl group or carboxy group substituted with a hydroxyl group); Substituted alkoxyl groups, others represent hydrogen atoms).
[2" claim-type="Currently amended] In the general formula (I),
R ¹ is an alkyl group having ¹ to 10 carbon atoms, and R ² is an alkoxyl group having 1 to 4 carbon atoms substituted with one or two hydroxyl groups or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group Anti-allergic agent of anti description.
[3" claim-type="Currently amended] In the general formula (I),
R ¹ is an alkyl group having ¹ to 10 carbon atoms and R ³ is an alkoxyl group having 1 to 4 carbon atoms substituted with one or two hydroxyl groups or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group Anti-allergic agent of anti description.
[4" claim-type="Currently amended] In the general formula (I),
R ¹ is an alkyl group having ¹ to 10 carbon atoms and R ⁴ is an alkoxyl group having 1 to 4 carbon atoms substituted with one or two hydroxyl groups or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group Anti-allergic agent of anti description.
[5" claim-type="Currently amended] In the general formula (I),
R ¹ is an alkyl group having ¹ to 10 carbon atoms, and R ⁵ is an alkoxyl group having 1 to 4 carbon atoms substituted with one or two hydroxyl groups or a 1 to 4 alkoxyl group substituted with one carboxyl group; Anti-allergic agent of anti description.
[6" claim-type="Currently amended] In the general formula (I),
R ¹ is an alkenyl group having 2 to 10 carbon atoms, and R ² is an alkoxyl group having 1 to 4 carbon atoms substituted with one or two hydroxyl groups or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group The antiallergic agent of Claim 1.
[7" claim-type="Currently amended] In the general formula (I),
R ¹ is an alkenyl group having 2 to 10 carbon atoms and R ³ is an alkoxyl group having 1 to 4 carbon atoms substituted with one or two hydroxyl groups or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group The antiallergic agent of Claim 1.
[8" claim-type="Currently amended] In the general formula (I),
R ¹ is an alkenyl group having 2 to 10 carbon atoms and R ⁴ is an alkoxyl group having 1 to 4 carbon atoms substituted with one or two hydroxyl groups or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group The antiallergic agent of Claim 1.
[9" claim-type="Currently amended] In the general formula (I),
R ¹ is an alkenyl group having 2 to 10 carbon atoms, and R ⁵ is an alkoxyl group having 1 to 4 carbon atoms substituted with one or two hydroxyl groups or an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group The antiallergic agent of Claim 1.
[10" claim-type="Currently amended] Benzopyran derivatives characterized by the general formula (II):

(Wherein R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms, any one of R ² , R ³ , R ⁴ and R ⁵ represents an alkoxyl group substituted with a carboxy group, Others represent hydrogen atoms).
[11" claim-type="Currently amended] In the general formula (II),
The benzopyran derivative according to claim 10, wherein R ¹ is an alkyl group having ¹ to 10 carbon atoms and R ² is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group.
[12" claim-type="Currently amended] In the general formula (II),
The benzopyran derivative according to claim 10, wherein R ¹ is an alkyl group having ¹ to 10 carbon atoms and R ³ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group.
[13" claim-type="Currently amended] In the general formula (II),
The benzopyran derivative according to claim 10, wherein R ¹ is an alkyl group having ¹ to 10 carbon atoms and R ⁴ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group.
[14" claim-type="Currently amended] In the general formula (II),
The benzopyran derivative according to claim 10, wherein R ¹ is an alkyl group having ¹ to 10 carbon atoms and R ⁵ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group.
[15" claim-type="Currently amended] In the general formula (II),
The benzopyran derivative according to claim 10, wherein R ¹ is an alkenyl group having 2 to 10 carbon atoms and R ² is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group.
[16" claim-type="Currently amended] In the general formula (II),
The benzopyran derivative according to claim 10, wherein R ¹ is an alkenyl group having 2 to 10 carbon atoms and R ³ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group.
[17" claim-type="Currently amended] In the general formula (II),
The benzopyran derivative according to claim 10, wherein R ¹ is an alkenyl group having 2 to 10 carbon atoms and R ⁴ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group.
[18" claim-type="Currently amended] In the general formula (II),
The benzopyran derivative according to claim 10, wherein R ¹ is an alkenyl group having 2 to 10 carbon atoms and R ⁵ is an alkoxyl group having 1 to 4 carbon atoms substituted with one carboxyl group.
[19" claim-type="Currently amended] Use of a benzopyran derivative represented by formula (I) or a physiologically acceptable salt thereof for the preparation of an antiallergic agent:

(Wherein R ¹ represents an alkyl group having 1 to 10 carbon atoms or an alkenyl group having 2 to 10 carbon atoms, and any one of R ² , R ³ , R ⁴ and R ⁵ is an alkoxyl group or carboxy group substituted with a hydroxyl group); Substituted alkoxyl groups, others represent hydrogen atoms).

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同族专利:

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公开号 | 公开日

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DE60203029D1|2005-03-31|

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US6670391B2|2003-12-30|

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AT289601T|2005-03-15|

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ES2233748T3|2005-06-16|

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CA2391239A1|2002-12-28|

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TWI224099B|2004-11-21|

---

CA2391239C|2009-01-20|

---

EP1273578B1|2005-02-23|

---

AU779232B2|2005-01-13|

---

EP1273578A1|2003-01-08|

---

AU4893902A|2003-01-02|

---

CN1473565A|2004-02-11|

---

US20030096860A1|2003-05-22|

---

DE60203029T2|2006-02-23|

---

KR100857841B1|2008-09-10|

---

CN1307991C|2007-04-04|

引用文献:

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

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法律状态:
2001-06-28|Priority to JPJP-P-2001-00196462

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2001-06-28|Priority to JP2001196462

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2002-06-26|Application filed by 다이니혼 잉키 가가쿠 고교 가부시키가이샤

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2003-02-25|Publication of KR20030015827A

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2008-09-10|Application granted

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2008-09-10|Publication of KR100857841B1

优先权:

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申请号 | 申请日 | 专利标题

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JPJP-P-2001-00196462|2001-06-28|

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JP2001196462|2001-06-28|