• 专利附录
  • 专利说明
  • 权利要求
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  • 引用文献
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  • 优先权
    • 专利摘要:
    New tetrazole derivatives of the general formula: <IMAGE> I [wherein R1 represents a halogen atom, a straight- or branched-chain alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl or alkylsulphamoyl group, each such group containing from 1 to 6 carbon atoms, a dialkylsulphamoyl, dialkylamino, or dialkylcarbamoyl group (wherein the two alkyl groups may be the same or different and each contains from 1 to 4 carbon atoms), a straight- or branched-chain alkanoyl, alkoxycarbonyl, alkoxycarbonylamino, alkylcarbamoyl or alkanoylamino group containing from 2 to 6 carbon atoms, a cycloalkylcarbonyl group containing from 3 to 8 carbon atoms in the cycloalkyl moiety, or a hydroxy, formyl, nitro, trifluoromethyl, trifluoroacetyl, aryl, benzyloxycarbonylamino, amino, sulphamoyl, cyano, tetrazol-5-yl, carboxy, carbamoyl, benzyloxy, aralkanoyl or aroyl group, or a group of the formula: -CR2=NOR3 II (wherein R2 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 5 carbon atoms, an aryl, aralkyl or trifluoromethyl group, or a cycloalkyl group containing from 3 to 8 carbon atoms, and R3 represents a hydrogen atom, or a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms optionally substituted by a phenyl group, or represents an aryl group optionally substituted by one or more substituents selected from halogen atoms and straight- or branched-chain alkyl and alkoxy groups containing from 1 to 6 carbon atoms and hydroxy, trifluoromethyl and nitro groups), and m represents zero or an integer 1, 2 or 3, the substituents R1 being the same or different when m represents 2 or 3] possess pharmacological properties, in particular properties of value in the treatment of allergic conditions.
    公开号:SU961560A3
    申请号:SU792760899
    申请日:1979-04-26
    公开日:1982-09-23
    发明作者:Энтони Рамсден Кристофер；Ноулес Филип；Джонатан Льюис Эдвард；Лант Эдвард；Эрнст Райт Дерек
    申请人:Мэй Энд Бейкер Лимитед (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to methods for the preparation of new tetrazene derivatives, which can be used in medicine.
    A known method for the preparation of tetrazolylcarboxylic acid amides by the reaction of tetrazole-5-carboxylic acid halides with phenyl derivatives * ·. Hafl ^
    The aim of the invention is a method for producing new tetrazole-5-carboxylic acid amides having foam pharmaceutical properties.
    The goal is achieved by the proposed method of obtaining arbitrariness. tetrazole by the general formula chain containing 2-4 atsma carbon, an alkoxycarbonyl group containing 2 or 3 carbon atoms, a cyclopropylcarbonyl group, a trifluoroacetyl 5 group or a phenylacetyl group;
    I represents hydrogen or a halogen atom, or an alkyl undeveloped group containing 1-3 carbon atoms, a methoxy group, a methylsulfonyl—] 0 group, an apetylamino group, a nitro or cyano group, go; their salts.
    The method is; that carry out the interaction of the compounds of General formula where R represents K! , N-dimethylcarbamide group, alkanoyl group with unbranched or ^ branched
    (Th)
    where R and have the indicated meanings, with the double-potassium salt of tetrazole-5-carboxylic acid in the presence of N, N-dimethyl (chloromethyleneimmonium) chloride or its £> 61560 source, and the target products are isolated in free form or in the form of salts.
    The process is usually carried out at (-25) (35) ° C.
    As a source, N, N-dimethyl · -; 5, (chloromethyleneimmonium) chloride use a mixture of an acid chloride, for example oxalic acid, and. dimethylformamide.
    In the compound of formula I, each hydrogen atom in the groups —OH, —NHCO, and —MH to can cause tautomerism, while all the resulting tautomeric forms are present in greater or lesser amounts and are in dynamic equilibrium with each other. fifteen
    Pharmaceutically acceptable salts and bases of the compounds of formula I are salts whose cations at therapeutic dosages are relatively harmless to the animal organism; therefore, the pharmacological properties of the starting compounds of formula T are not impaired by the side effects of these cations. Such salts include alkali metal salts, for example sodium or potassium, 25 ammonium salts and amine salts, applicable in pharmacology, for example, ethylenediamine, choline, diethanolamine, triethanolamine, octadecylamine, diethylamine, triethipamine, 2-amino-2- (hydroxymethyl) -propan-1,3-dirl 30 and 1- (3,4-dioxiphenyl) -2-isopropylaminoethanol.
    The proposed tetrazole derivatives possess important pharmacological properties, especially valuable for 35 treatment of allergic diseases, for example, respiratory tract disorders, such as those caused by the interaction of antibodies in tissues with specific 4 O antigens, such as, for example, allergic bronchial asthma.
    Particularly important are those compounds of formula Ϊ in which R is dimethyl carbamoyl, acetyl, propionyl, butyryl, isobutyryl, methoxycarbonyl, ethoxycarbonyl, cyclopropylcarbonyl, trifgoracetype or phenylapetyl and R * is as defined herein and their pharmaceutically acceptable salts.
    Among the compounds of the formula I, which are particularly specific, are:
    3'-Acetyl-2 * -oxy-5-methyltetrazole-5-carboxanil1u1 (A);
    3 * —Acetyl-5 * ethyl-2 * -oxytetrazole-5-carboxanipide (B); f
    3 * Acetyl-2 * -oxy-5-nitrotetrazole-5-carboxanplide (C);
    55,
    3 * -acetyl-5 * 1 -acetylamin-2 * - oxytetrazole-5 — carboxanilide (D);
    2 1 -Oxy-3 —isobutyryl — 5 * —methyl tetrazol-5 — carboxanilide (E);
    3'-Apetil-5 X -pian-2 z -oxytetrazole-5-carboxanilide (F);
    3'-cyclopropylcarbonyl-2 / -oxy-5 * -methyl tetrazole-5-carboxanilide (G);
    - Oxides — 5 * —methyl — Z 1 —trifluoroacetyl — tetrazole-5-carboxanilide (H);
    Acetyl-5-fluoro-2 T '/ -oksi'gtrazol -karboksanilid-5- (j);
    3 ** - Acetyl — 5 * —Bromine — 2 1 —oxytetrazole — 5 — carboxanilide (!);
    3'— Acetyl — 2 * —oxy — 5 / —methoxy tetra-zol-5-carboxanilide (K);
    5 * -Pian-2 hydroxy-3-propionyltetrazole-5-carboxanilide (b);
    2 * -Oxy-5 * -methyl-3 * -phenylanethyltetrazole-5 ~ carboxanilide (M);
    3 ' -acetyl-2 - ok si-5 * methylsulfo nyltetrazop-5-carboxanipide (O);
    -Butyryl-2-hydroxy-5 , methyltetrazole-5-carboxanilide (P);
    ( 3 Ζ - (Ν, M-dimethylcarbamoyl) -2 / -oxy-5-methyltetrazole-5-carboxanilir (0.);
    -Oxy-3 '—methoxycarbonyl — 5 — methyltetrazole-5-carboxanilide (R);
    3 t - Ethoxycarbonyl-2 * -oxy-5'-methyltetrazole-5-carboxanilide (S);
    3 * -acetyl-2 * -oxy-5 * -propyltetrazole-5-carboxanilide (T);
    3 * -acetyl-4-hydroxytetrazole-5 — carboxanilide (U): ' (
    5 * -ethyl-2 -oxy-3-propionyltetrazole-5-carboxylic acid anilide (V);
    2'-hydroxy-5-methyl-3 * -propioiyl tetra’sol-5-carboxanilide ( </); and their pharmaceutically acceptable SALTS;
    In pharmacological trials, the new compounds suppress the passive skin anaphylactic (PCA) reaction / caused by the combination of tissue-bound reactin antibodies with antigenic substance (reagin-allergenic interaction); they are carried out according to the method described by Ogilvy. For these tests, the serum is taken from rats that were infected with the larvae of the Nippos-brongy nematode parasite (jUjiVroviCietisisJB as a result of the infection with the parasite / animals receive subcutaneous injections of appropriate dilutions of such serum, and then after 48 hours they are given an intravenous allergenic substance along with Evans blue dye,
    An allergenic substance is a liquid that pops up after centrifugation of homogenates of adult Nipposironjpftjs - worms, which are softened in Tyrode's solution. Sites of the PCA reaction are visually determined by the distribution of the Evans blue dye as a result of increased capillary> permeability 1 due to the release of the biologically active substance.-j in cells where the allergen interaction occurred. New compounds, when administered intravenously immediately before the injection of the allergen or after oral administration 30 minutes before the introduction of the allergen, prevent the development of the PCA reaction.
    In the table. 1 daNa intravenous dose in mg / kg of animal weight, which causes 100% inhibition of the PCA reaction (UNIT 100)
    In the table. 2 - oral dose in mg / kg of animal weight, giving a 50% inhibition of the PCA reaction (ED-50).
    Table 1 Compound ED 100, could / kg (intravenously) BUT 0.01 AT 0.01 FROM 0,0 £ E 0.02 F 0.01 G 0.02 E 0.010.05 TO 0.01 L 0.02 R 0.05 Q 0.02 R 0.05 S 0.01 t 0.01 υ 0.005 • at 0.01 V / 0.02
    ί
    061560
    table 2
    Compound E D 50 mg / kg j (oral) 5 BUT 0.06AT 0.19FROM 0.04 10 E 3.2. F 0.4R. 5,6 fifteen S 3.6t 0.46υ 0.06V 1.3 twenty i w 0.88
    The use of the compounds of formula I is convenient in that they are very slightly toxic to mammals. For example, compounds A and C were administered orally to mice at doses of 100 mg / kg of the animal’s body weight, even after 3 days such large doses were not induced. death of an animal.
    Example 1. Compound B. A solution of dry dimethylformamide (1.5 ml) in dry acetonitrile (3.6 ml); at - 20 ° C, it is treated dropwise with stirring with a solution of acid chloride of oxalic acid (0.53 ml) in 0.6 ml of dry acetonitrile. The resulting white suspension is stirred at −20 ° C. for 15 minutes, then treated with the double-potassium salt of tetrazole-5-carboxylic acid (1.14 g), and the mixture is stirred at −20 ° C. for 20 minutes. The resulting mixture was treated with a solution of 3-amino-5-type-2-hydroxyacetophenone (1.08 g) in 2 ml of dry * pyridine, allowed to warm to room temperature and stirred for 20 hours. Then the mixture was treated with a mixture of 30 ml ; dichloromethane and an aqueous solution of sodium carbonate (20 ml, 2 N). Dichloromethane 50 1 layer was separated, the aqueous layer was washed with another 20 ml of dichloromethane and acidified to pH 1 with concentrated hydrochloric acid. The obtained orange precipitate g is filtered off, washed with water, crystallized from ice-cold acetic acid over 55 ; acid (20 ml) and get Z'-acetyl — 5-ethyl-2 / —oxypatrazole-5-carboxane ”LID (0.55 g) with so pl. 243-245, S.
    061860
    Example 2. Compound B.
    A mixture of Ν, H / dimethyl (chloromethyleneimmonium) chloride (0.26 g), dicalcium salt of tetrazo l-5-carboxylic acid (0.38 g) and 15 ml of dry dimethylformamide is stirred at room temperature for 30 minutes. 3-amino-5-ethyl-2-hydroxyapetophenone (0.36 g) was added and the mixture was stirred at room temperature overnight. A mixture of 20 ml of dichloromethane and 20 ml -2 N. a solution of bi * *, sodium carbonate; the mixture is carefully webbal * 1 there are and the aqueous layer is separated. The dichlorome * tan layer is again washed with 20. ml of 2 N. aqueous sodium bicarbonate 15 '. The aqueous layers are combined and acidified to pH 1 with concentrated hydrochloric acid. Get 3'-acetyl-5 ethyl - -2 '-oxytetrazole-5-carboxanilide (0.12 g) with so pl. 240-242 ° C .. 20
    Following the procedure described in the preceding examples and using the corresponding starting materials of general formula 1, one obtains: 25
    3'-Acetyl-2 f -oxy-5'-methyltetrazole--5-carboxanilide; 257 ° C (decomp.) ^
    3 * -acetyl-2 1 -oxy-5 1- nitrotetrazr * * -5-carboxanilide with mp 239-240 ° C (decomp.); Z
    3 * -acetyl-5 * -acetylamino-2-hydroxytetrazole-5 — carboxanilide with mp 270271 ° C (diff.);
    2 * -Oxy-3 ’—isobutyryl-5 '-methyl tetrazole-5-carboxanilide; 224-225 ° C (various);
    3 * -Apetil-5 g- cyano-2-hydroxytetrazole-5-carboxanilide with mp 270—274 ° С (decomp.); f '-cyclopropylcarbonyl-2-oxy-b'— methyltetrazole-5-carboxanilide with so pl. 261-263 ° C (decomp.);
    2 1 -Oxy-5'-methyl-3 ^ -trifluoroacetyltetrazole-5-carboxanilide with mp 248249 ° C (decomp.);
    3 '—Acetyl-5'-fluoro j * -2 z- oxiteter ^ zo ^ * -5 — carboxanilide with so pl. 237-239 C (decomp.);
    ’-Acetyl-5-bromo-2 '—oxytetrazole — 5-carboxanilide with mp 252-254 ° C (decomp.);
    3 ’-Acetyl-2 * —oxy-5 — methoxy tetra-zol — 5 — carboxanilide with mp 251—253 ° С (decomp.);
    5 '-Piash> -2 ’-oxy-3-propionyltetra-h eol-5-carboxanilpd with mp 257—259 ° С (decomp.); ’
    2'-hydroxy-5-methyl-3-phenylacetyltetrazole-5-carboxanilide with the like 2O2 Q C (decomp.)
    3 'Acetyl-2' -hydroxy-5 x -metilsulfoniltetrazol-5-carboxanilide with aphids. 256,259 ° C (various);
    Z'— Butyryl-2 ’—oxy-5’ -methyl tetraz ol-5 — carboxanilide with mp 231-233®C (various);
    3— (N, Ν-dimethylcarbamoyl) -2'-oxv-5'-methyltetrazole-5-carboxanilide with mp 235 ° C (decomp.);
    2 1 -Oxy-3 '-methoxycarbonyl-5 { -methyltetrazole-5-carboxanilide so pl. 238240 ° C;
    3'-Ethoxycarbo nil-2 g- oxv-5 1- methyltetrazole-5-carboxanilide with mp 252,254 ° C (decomp.);
    3 1- Acetyl-2 '-oxy-5' -propyltetrazole-5-carboxanilide with so pl. 179-180 ° C · (decomp.);
    3 ’-Acetyl-2’-oxytetrazole-5-carboxanilide with so pl. 239-241 ° C (decomp.);
    Ethyl 2 * -oxy-3 '-propionyltetrez-5-carboxanilide with mp 225-226 ° C (decomp.);
    2 * -Oxy-5 ’-methyl-3 — propionyltetrazole-5 — carboxanilide (decomp. From ethanol).
    with mp 230-232 ° C
    权利要求:
    Claims (2)
    [1]
    36b is consumable, and the desired products are isolated in free form or in the form of snakes. The process is usually carried out at (-25) (35) С. As a source of N, N-dimethyl -; (chloromethylenimmonium) chloride uses a mixture of an acid chloride, for example oxalic, and dimethylformamid. In the compound of formula I, each hydrogen atom in pears -OH, -INSO, and -MH can induce tautomerism, with all the resulting tautomeric forms present in greater or lesser amounts and in dynamic equilibrium with each other. Pharmaceutically acceptable salts and bases of the compounds of formula 1 are salts whose cations at therapeutic dosages are relatively harmless to the organism of animals, therefore the pharmacological properties of the starting compounds D are not impaired by the side effects of these cations. Such salts include alkali metal salts, for example sodium or potassium, ammonium salts and amine salts, applicable in pharmacology, HanpHViep ethylenediamine, choline, diethanolamine, triethanolamine, octa decylamine, diethylamine, triethylamine, 2-amino-2- (oximetx1) -propan-1,3-dirla and 1- (3,4 "dioxyphenyl) -2-isools of ethanol. The proposed tetrazole derivatives have important pharmacological properties, especially valuable for the treatment of allergic diseases, such as respiratory disorders, such as those caused by the interaction of antibodies in tissues with specific antigens, such as allergic bronchial asthma. Particularly important are those compounds of formula 1 in which R is dimethyl carbamoip, aietil, propyl shh, buttfkl, isobutyryl, metroxycarbonyl, ethoxycarbonyl, cycloprophylcarbonyl, trifroprocetyl or fenipacetyl and R corresponds to the specified patterns, and their combinations, and to match the matching facial patterns, and their heart patterns and theirfy combines will match their heart patterns, and their heart patterns and their components will be used to match their heart patterns, and their heart patterns and their components will be used to match their heart patterns, and their heart patterns will be the same as the ones you use and the heart combinations you use to make your home life. Among the compounds of the formula I, which are of particular importance, are: C-Acetyl-2-hydroxy-5-methyl tetrazole-5-carboxyl shaps (A) ;. h -Atsetiz-B -vtvl-2-oksitetrazol-5ncarboxanilide (B); S -Attsish -2 -OKCW-5 -shggrotetrazol 5-carboxate (C); 3-Acetyl-5-acetylamine-2-oxytetazol-5 carboxase; (D); 2 -OxN-3-isobutyryl-b-methyltet aaol-5-carboxac1ID (E); 3-Acetyl-5-cyan-2-oxytetraaol-5 carboxanilide (F); 3-Cyclopropylcarboyl-2-oxy-3 methyltetrazolg-carboxanilide (G); 2 - “QsHuH-S-methyl-3-trifluoroacetyp-tetrazole-5-carboxanilide (H); Z-Apetip b-fluoro-2-toxic trazol-5carboxanilide (d); 3'-Acetyl-5-bromo-2-oxitvrazo 5-carboxanilide (J); 3 -Adetil-2-oxy-5-methoxytetra-ol-5-carboxanilide (K); 5-11ian-2 ox-No-3-proshynuyl tetrazole-b-carboxaneshgid (b); .. 2-Oxo-5-methyl-3-phenylacetyl tetraol-W-carboxanewiches (M); 3-Adetyp-2-ox-5-methylsulfonyl 1 tetrazo-5-carboxanilide (O); h -Butyrene-2 -oxy-5-methyltetrazo # 5-carboxanilide (P); 3 (M, K / -Dimetypcarbamoyl) -2-hydroxy-5-methyltetrazol-5-carboxaniphs (and) 2-Ox-i-3-methoxycarbonyl-b-methyptetrazole-5-carboxanilide (R); 3-Ethoxycarbonyl-2-OKCW-5-methylb-interrazol-3-carboxanilide (S); 3-Acetyl-2-sgc-5-propyl-tetrazole-5-carboxanilide (T); 3-Acetyl-4-oxytetrazol-5-carboxanilide (s): B-EtiJ -2 -oxy-3-propionyl tetrazole-5-carbo and anilide (V); 2-Oxy-5-methyl-3-propionyltetrazole-5-carboxacshid (); and their pharmaceutically acceptable. Solig In pharmacological tests, new compounds suppress the passive skin anaphylactic (XRD) reaction / caused by combining reagin antibodies fixed in tissues with an antigenic substance (reagin-allergenic interaction); they are carried out according to the method described by Ogilvy t. For these tests, serum was taken from rats that were infected with the larvae of the nematode parasite Nipposirorg-yyi5, Hypertelye115 5B, as a result of the infection with the parasite, reagent antibodies are erupted in the host animal and are found in the serum selected in the animal serum and found in the animal serum, found in the animal serum and found in the animal serum, found in the animal serum, found in the animal serum, found in the animal serum, found in the host serum. Other, not ejected animals, receive subcutaneous injections of COOT with the appropriate dilution of this serum, and then after 48 hours intravenous they are given an allergic substance along with beets Evavs dye. Kotopux worms soften in Tyrode's solution. PGA sites are visually determined by the prevalence of the blue Crasptel Evavs as a result of the increased capillary I-viability of the release of biologically active ve. the cells in the cells where the reagin occurred allergenic interaction. When intravenously injected immediately before the injection of the vans allergen after the oral administration has been administered for an hour and 30 minutes before the administration of allergen, new compounds prevent the development of the PCA reaction. In tab. 1 daVa intravenous dose in mg / kg body weight of the animal, which induces 100% inhibition of the XRD reaction (AU 100) .. In Table. 2 "oral dose in mg / kg of the animal's weight, dakhtsa 50% ivsh-reaction reaction XRD (ED-50). . Table 1 0 The use of compounds of the formula I is convenient in that they are very little toxic to mammals. For example, Au and C compounds were orally administered to mice at doses of 100 mg / kg animal body weight, and even after 3 days such large doses were not induced. death of an animal. Example 1. Compound B. A solution of dry dvmethylformamide (1.5 ml) in dry acetic nitrile (3.6 ml) at 20 ° C is treated dropwise with stirring with a solution of chlorine hydrochloride oxalic acid (0.53 ml) in / O, 6 ml dry acetonitrile. The resulting white suspension is stirred at –20 ° C for 15 minutes, treated with a two-potassium salt of tetrazole-5-carboxylic cake (1D4 g), and the mixture is stirred at –20 ° C for 20 minutes. The mixture was treated with a solution of 3-amivx-5-etyp 2-Obsvacetophenone (1.08 g) in 2 ml of dry pyridine, allowed to warm to room temperature and stirred for 2 oh. The mixture was then treated with a mixture of 30 ml of dichloromethane and an aqueous solution of sodium carbonate (20 ml, 2 n.). The dichloromethane layer is separated, the layer is washed with another 20 ml of dichloromethane and the acid; to pH 1 with concentrated hydrochloric acid. An orange precipitate is washed off with water, washed with glacial acetic acid (20 ml) and recrystallized with glacial acetic acid (20 ml) to give 3-acetyl-5-etip-2 / h of etrazol-5-carbox in LID (O, 55 g) with T.PL. 243-24SPC. Example
    [2]
    2. Compound B. Oles N, K / -dg metyp {5Shormetipet1L monium) chloride (0.26 g), two-potassium salt of tetraaol-5-carboxylic acid (0.38 g) and 15 ml of dry dimethyl form amide are stirred at room temperature ZO min. 3-Amino-5 ethyp-2-oxyacetophenone (0.36 g) is added and the mixture is stirred at room temperature overnight. A mixture of 20 ml of dyshormethane and 20 ml of 2N is added. sodium bicarbonate solution; Wash carefully and the aqueous layer is separated. The dichlorum tan layer is washed again with 20 ml. 2 n. an aqueous solution of sodium bicarbonate. The aqueous layers are combined and acidified to pH 1 with concentrated hydrochloric acid. H-acetyl-b-ethyl-2 oxytetrasol-5-carboxanilide is obtained (OD 2 with mp 240-242 ° C. Following the procedure described in the preceding examples, and using the corresponding starting materials of general formula 1, we obtain: 3-Acetyl-2-oxy-b-methyltetrazol-5-carboxacshshid with mp. (Decomposed 3 -Acetyl 2-hydroxy-b -nitrotetrazole -B-carboxanilide with mp. 239-24 ° C (rael) 3 -Aceti - b -vcetylamino-2-oxytetraaol-b-carboxanilide with mp 27O271 C (decomp.); 2 -Oxy-3-isobutyryl-3-metiptetra rozop-B-carboxanil with mp 224-22b with (de .); 3-Apetip-b-1shano-2-oxyterazolp-5-carboxanilide with mp 270-274 C (decomp.) s-Cyclopropycarbonip-2 methyltetrazol-5-carboxanilide with a TP of 261-263 s (decomp.); 2 -Oxy-b -methyl-3-Trvfluorodetiptetrazol-b-carboxanipide with a mp of 248249 ° С (decomp.); 3-Adetiz-b-fluto 2-oxyterazo ;.-carboxylic acid Ipl. with t. P. 237-239 C (decomp.); 3-Acetyl-b-bromo-2-oxitrateraz-b-carboxaxide with t .pp. 252-2b4 C (decomp.); 3 -Acetyl-2-oxy-b-me1zhsitetrazol-b-carboxachogad with mp. 261-2b3 C (decomp.); b-Ciash -2-proshyushshtvtrach Zop β-carboxanilide with so pl. (razp.); 2gOx -b-methyl-3-phenylaptagenter zop-bnviarboxanzlzd with T.mi. (3 times -Acetyp-2-ox-n-b-x-xcpsulfonyltetraeol-b- "arboxvnilide with TJBI. 266269 C (decomp.); 3-Butyryl-2-oxb-b-methyltetrazol-b-arboxanilide with mp. 231-233 C (Raal.); 3- (M, N-imethylcarbamoyl) -2-oxy-5-methyl-tetrazole-b-carboxanipide with mp 23b ° C (dec.); 2-Oxy-3-methoxycarbonip- b -methyltetrazol-b-carboxanilide with a melting point of 23 240 240 C; H-ethoxycarbonip-2-oxb-b-methnptetrazop-b-carboxeshgad with m.p. 262254 C (decomp.); h -Acetyl-2 -proshtetetrazole -b-carboxanipid with a melting point of 179-180 C (decomp.); h -Aceti-2 -2 -oxctetrazol-b-quartine on sanilide with Т.1Ш. 239-241 С (decomp.); b-Ethyl-2 -bksi-3-propioltgetrazol-b-ka rboxanilide with a melting point of 225-226 C (decomp.); 2 -Oxy-b - 1-type-3-propionyl tetra-ox-b-carboxyl with a mp of 230-232 C (decomp. from etavo w). Formula invented The method of obtaining tetra-ash derivatives of the general formula 1 OH H N N .. To -LA /, where R is an N, X. Methylcarbamoyl group, alkanoyl rpyib, an unbranched or branched chips pu, containing 2-4 carbon atoms, alkoxycarbonyl group containing 2 or 3 carbon atoms, a roauionpa-J pilcarbonyl group, a trifluoroacetate group or a phenylacetyl group; R) are hydrogen or a halogen atom, or an unbranched alkyl group containing 1 to 3 carbon atoms, a methoxy group, a methyl sulfone group, an adhyl group, a nitro group. The 1iEnn cyano group, or their salts, is distinguished by If and also by the fact that it is possible to interact (a common compound of the formula P
    9bb15vOiio
    where R and R have the indicated meanings, Sources Iyformatsh,
    with dikalievoy sopy tetrvzop-5-karbovo-.printye in vvvvavavie during examination
    acid in pre-M, K-dimetvp-. 1. US patent Ma 3966965, (hloumetipekimmoiy) chloride or himkl. 424-269, published. 1976.
    source, and target products allocate 5 2. Dwn u "oPo v. 1967, 12, p. 112 in free form or in the form of salts.131.
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    KR900001174B1|1990-02-27|Process for preparing thioketen derivatives
    US3903276A|1975-09-02|N-carboxymethyl-N-substituted glycinate esters of 3-hydroxy-1,4-benzodiazepin-2-ones for inducing a calming effect
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    同族专利:
    公开号 | 公开日
    CH635832A5|1983-04-29|
    CA1118427A|1982-02-16|
    IE47960B1|1984-08-08|
    SU1494866A3|1989-07-15|
    US4442115A|1984-04-10|
    HK95784A|1984-12-14|
    ZA786056B|1979-10-31|
    IE782118L|1979-04-28|
    LU80436A1|1979-06-15|
    FR2407207B1|1981-12-18|
    FR2407207A1|1979-05-25|
    IT1099538B|1985-09-18|
    BE871623A|1979-04-27|
    DE2846931A1|1979-05-10|
    DK476978A|1979-04-29|
    MY8600719A|1986-12-31|
    AU517502B2|1981-08-06|
    SG54284G|1985-03-08|
    HU177857B|1981-12-28|
    NL7810634A|1979-05-02|
    IT7829145D0|1978-10-26|
    SU1080745A3|1984-03-15|
    DE2846931C2|1988-12-01|
    JPS5470274A|1979-06-05|
    AU4109378A|1980-05-01|
    JPS6216949B2|1987-04-15|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    AR207563A1|1973-03-23|1976-10-15|American Home Prod|PROCEDURE FOR PREPARING A NEW OXAMIC ACID ESTER|
    US4039672A|1975-01-11|1977-08-02|Societe D'etudes Scientifiques Et Industrielles De L'ile-De-France|N- 2-methoxy 4,5-azimido benzamide and its pharmaceutically acceptable salts|
    GB1547564A|1975-06-05|1979-06-20|Lilly Industries Ltd|Acylated amino-heteroaryl compounds|
    US4069153A|1975-10-28|1978-01-17|American Sterilizer Company|Method of destroying pyrogens|
    US4013647A|1976-03-23|1977-03-22|American Home Products Corporation|Morpholine containing tetrazole-5-carboxamide derivatives|
    GB1561350A|1976-11-05|1980-02-20|May & Baker Ltd|Benzamide derivatives|EP0065874A1|1981-05-22|1982-12-01|Ono Pharmaceutical Co., Ltd.|2-Aminophenol derivatives, methods for their preparation and composition containing the same|
    GB8333665D0|1983-12-16|1984-01-25|Lilly Industries Ltd|Organic compounds|
    EP0165897B1|1984-05-24|1989-03-15|Ciba-Geigy Ag|Resorcin ethers|
    CH665637A5|1984-12-24|1988-05-31|Wakamoto Pharma Co Ltd|5-TETRAZOLE AS ANTIASTHMATIC AGENT, COMPOSITION CONTAINING IT AND PROCESS FOR PREPARING THE COMPOSITION.|
    ZA865091B|1985-07-22|1988-02-24|Riker Laboratories Inc|Substituted di-t-butylphenols|
    PT81492B|1985-09-17|1988-03-03|Ciba Geigy Ag|METHOD FOR PREPARING NEW FLORORATED RESORCINE ETEREES|
    US4808604A|1985-10-03|1989-02-28|Ciba-Geigy Corporation|N- tetrazol-5-yl carboxamides and anti-allergic use thereof|
    PT81374B|1985-10-25|1988-02-17|Ciba Geigy Ag|PROCESS FOR THE PREPARATION OF NEW ETERES OF RESORCINE|
    JPH0579063B2|1986-08-12|1993-11-01|Wakamoto Pharma Co Ltd|
    JPH0271838U|1988-11-18|1990-05-31|
    JPH0273627U|1988-11-24|1990-06-05|
    GB9302331D0|1993-02-05|1993-03-24|Smithkline Beecham Plc|Process|
    FR2788691B1|1999-01-21|2002-06-14|Oreal|COMPOSITIONS FOR OXIDATION DYEING OF KERATINIC FIBERS COMPRISING A CATIONIC COUPLER, NOVEL CATIONIC COUPLERS, THEIR USE FOR OXIDATION DYEING, AND DYEING METHODS|
    FR2788768B1|1999-01-21|2001-02-16|Oreal|NOVEL CATIONIC 2-ACYLAMINOPHENOLS, THEIR USE AS A COUPLER FOR OXIDATION DYE, COMPOSITIONS COMPRISING SAME, AND DYEING METHODS|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB4509777|1977-10-28|
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