• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The present invention relates to new potent membrane stabilizing compounds of the formula <CHEM> wherein R<1> is alkoxyalkyl, hydroxyalkyl or alkyl, which alkyl groups may be branched or straight, R<2> is halogen or hydrogen, R<3> is hydrogen or alkyl, R<4> and R<5> are same or different and are each hydrogen, alkoxy, alkyl, alkoxyalkyl, cyano, or hydroxy, n is 0, 1, 2, or 3, and X is -O-, -CH2-, or @ The present compounds are potent heart antiarrhythmic agents possessing membrane stabilizing effect and beta -receptor blocking effect in same clinical doses. The compounds are used in treating antiarrhythmic conditions, but can also be used in the treatment of hypertension, angina pectoris, or nervous heart. The invention also relates to processes for preparing the compounds, method of treating antiarrhythmic conditions and pharmaceutical preparations containing said compounds.
    公开号:SU860692A1
    申请号:SU802921298
    申请日:1980-05-15
    公开日:1981-08-30
    发明作者:Виллиам Бирнес Юджин；Бенни Роджер Самуэльссон Густаф；Карл Гуннар Айберг Аксель
    申请人:Аб Хессле (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to a process for the preparation of novel aminopropanol derivatives or their salts with p-blocking activity. Known method 1 for the preparation of aminopropanol derivatives of the general formula OH. -CH CH-CHj-NH-CHj-CH where Z is alkyl, chloro, cyano, hydroxymethyl, acetyl or o-allyl, by reacting a compound of formula 2i-C- / ° g CH-CH2-H1 with 3, 4-dimethoxyphenethylamine CHjO CHzO-f VcHj-CHi-NHj Known compounds exhibit A-blocking activity. The purpose of the invention is to obtain new derivatives of aminopropanol or their salts, expanding the arsenal of means of action on a living organism. This goal is achieved, based on the well-known reaction of the present method of preparing a compound of the formula IZ OCH, CHOHCH, NH-CH- (CH, n-0-f-Ux p, where R, is alkoxyalkyl with 2-4 carbon atoms, oxyalkyl with carbon atoms 1-4 and alkyl with 1-4 carbon atoms; R2. - halogen, hydrogen; Ra - hydrogen, alkyl with 1-4 carbon atoms; f (Rg - are the same or different and mean hydrogen, alkoxy with the number of atoms carbon 1-4, alkyl with the number of carbon atoms 1-4, alkoxyalkyl with the number of carbon atoms 2-4, cyano, hydroxyl; n is an integer of 0-3 or their salts, which is It is concluded that a compound of the formula OCHjCHOHCHjlIH-CH-fCHajn-Z B, where R, R / j, R 3 and n have the above values, and Z means a reactive ester-esterified hydroxyl group, is coupled with the general formula wherein R and R5 are as defined above, followed by isolating the desired product in free form or as a salt. When using a reactive ester as the starting compound, the reaction is preferably carried out in the presence of a basic agent and / or an excess amine but. Suitable basic agents are, for example, alkali metal hydroxides (sodium or potassium hydroxide), alkali metal carbonates (potassium carbonate) and alkali metal alcoholates (sodium methoxide, potassium ethylate, potassium t.-butoxide). The reaction is carried out in an autoclave at 80-100 s in alkanol containing 1-3 carbon atoms. Example. 2.4 g of sodium are dissolved in 100 ml of ethanol, after which 9.4 g of phenol and 28.7 g of 1- (2-chloroethylamine) -3- (4- (2-methoxyethyl) phenoxy) propanol are added successively. -2 The mixture is heated in an autoclave on a boiling water bath for 10 hours. It is then filtered and the filtrate is evaporated to dryness. The residue is treated with 2 N. w at room temperature for one hour, extracted with ether, the aqueous phase is made alkaline with ammonia and extracted with ether. The ether phase of magnesium sulfate and the resulting 3- (2-phenethylamino) -1- (4- (2-meth hydroxyethyl) phenoxy) propanol-2 is transferred to the hydrochloride. Output 12.9 g (34% of theory), so pl. 1b2s (HCI). Similarly, 1.3- (2-meth-2) -4-hydroxyphenyl- (ethylamino) -1- (4) -methoxyethyl- (2-bromophenoxy) propane nol-2, m.p. (HCL), yield 40.8% of theory; II.3- (1-methyl-2) -4-hydroxyphenyl (e-Eylamino) -1- (4) -2-methoxyethyl (2-chlorophenoxy) -propanol-2. square (HCI), yield 44% of theory; III.S-Phenylmethylamino-1- (4-methoxymethylphenoxy) -PrO11anol-2, pl., 170.5-171, IV. 3 - (; 2-phenethylamino) -1- (4methoxymethylphenoxy) -propanol-2, pl. 169-169, (HCI); (F nilbutylamino) -1- (4methoxymethylphenoxy) -propanol-2, pl. 154-155s (HCI); Vi. H-Phenylmethylamino-1- (4) -2-methoxyethyl- (phenoxy) -propanol-2, mp. 162.5-164 ° C (HC); VII. 3- (3-phenylpropylamino) -1 (4) -2-methoxyethyl- (phenoxy) -propaol-2, so pl. (HCI); VIII.3- (4-phenylbutylamino) -1 (4) -2-methoxynstil - (phenoxy) -propaol-2, so pl. 143-14T; 5c (HCI); IX.3- (2) -3,4-dimethoxyphenyl (ethylamino) -1- (4) -2-methoxyethyl (phenoxy) propanol-2, mp. (HCO; X.3- (2 phenoxyethylamino) -1- (4) 2-methoxyethyl- (phenoxy) -propanol-2, mp. 83 ° C; XI.3- (4) -3,4-dimethoxyphenyl ( butylamino) (4) -2-methoxyethyl (phenoxy) propanol-2, mp 135c; XII.1- (2) -phenylethylamine- (3) 4- (3 methoxypropyl) (phenoxy) -2-propanol, t mp 167.5-168.5 ° C; XIII.3- (2-phenylethylamino) -1- (4) -2-methoxyethyl- (phenoxy) -propanol-2, mp (HC (); XIV.3- (2) -4-hydroxyphenyl- (ethylamino) -1- (4) -2-methoxyethyl- (phenoxy) -propanol-2, mp 160s (HC1); XV.3- (2- phenethylamino) -1- (4-2-methoxyetium) -2-bromophenoxy-propanol-2, mp 139 (tartrate). Biomedical studies show that aminopropanol derivatives are cardioselective p-receptor antagonists with a higher b-blocking activity than the known ones. The results of the studies are tabulated. Alprenol-1-isopropylamino-3- (2-allylphenoxy) propanol is studied as other well-known analogs -2; Draktolol-1-isopropylamino-3- (4-acetamidophenoxy) -propanol-2; metoprolol-1- (isopropylamino-3) -4- (2-methoxyethyl (phenoxy) -propanal-2; O-propranolol-1-isopropylamino-3-1- (naphthoxy) -propanol 2; lidocaine-diethylamino-2,6 xylidide
    1. A process for the preparation of aminopropanol derivatives of general formula I
    Vz OSI, snonsn gaz- (d), - o f
    where R is alkoxyalkyl with the number of carbon atoms from 2 to 4, oxyalkyl with the number of carbon atoms from 1 to 4 and alkyl with the number of carbon atoms from 1 to 4;
    R is halogen, hydrogen;
    R q is hydrogen, alkyl with 1 to 4 carbon atoms;
     5 are identical or different and mean hydrogen, alkoxy with the number of atoms of the carbon from 1 to 4, al-
    alkoxyalkyl with the number of carbon atoms from 2 to 4, iianogroup, hydroxyl,
    p is an integer of 0-3 or their salts, characterized in that the compound is
    Formulas II, 8 ,,
    oCH, CHOHCHira-cH- (cHi) n-z
    where R., Rj, R di n have the above values, and Z means a reactive ester-esterified hydroxyl group, is reacted with a compound of the general formula III
    ™ / 7 where yd and ry are as defined above, with a subsequent release of the desired product in free form or as salt. 8606928 Sources of information taken into account during the examination i. U.S. Patent 3,857,891, Cl. C 07 C 93/06, published 1968.
    权利要求:
    Claims (1)
    [1]
    Claim
    1. The method of obtaining derivatives of aminopropanol of General formula I
    In 3
    OCH, CH0HCH t NH- CH- (CH, L - о 4
    IN:
    where R, is alkoxyalkyl with the number of carbon atoms from 2 to 4, hydroxyalkyl with the number of carbon atoms from 1 to 4 alkyl with the number of carbon atoms from up to 4;
    - halogen, hydrogen;
    R 3 is hydrogen, alkyl with the number of carbon atoms from 1 to 4;
    K 4 And r 5 are the same or different and mean hydrogen, alkoxyl with the number of carbon atoms from 1 to 4, alk - with the number of carbon atoms from 1 to 4, alkoxyalkyl with the number of carbon atoms from 2 to 4, ianogroup, hydroxyl, η - integer 0-3 or their salts, characterized in that the compound of the general formula I 1 In 3 oc ^ cwcHpm-cH-icHtJn-ζ "1 where R ^, R 2 , RjH 'η · have the above meanings, a Ζ means a reactive, esterified 40 hydroxyl group is reacted with a compound of general formula JII
    S5 where id. and Ry have the above meanings, with subsequent isolation of the target product in free form or in the form of a salt.
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DD80923A|
    FR4851M|1964-08-12|
    FR2119843B1|1970-12-28|1974-03-22|Laroche Navarro Labo|
    FR2119844B1|1970-12-28|1974-03-22|Laroche Navarro Labo|
    ZA754241B|1974-11-01|1976-06-30|Haessle Ab|New amines|JPS6215062B2|1979-03-20|1987-04-06|Kyowa Hakko Kogyo Kk|
    DE3125870C2|1980-07-09|1994-09-15|William John Louis|3-aminopropoxyphenyl derivatives, their preparation and medicaments containing them|
    US4410548A|1980-07-09|1983-10-18|Reckitt & Colman Products Limited|Propanolamine derivatives|
    JPH0318607B2|1980-07-09|1991-03-13|Jon Ruisu Uiriamu|
    FR2497194B1|1980-08-07|1985-06-14|Sandoz Sa|NEW PHENOLIC COMPOUNDS|
    GB8519154D0|1985-07-30|1985-09-04|Ici Plc|Aromatic ethers|
    DE3544172A1|1985-12-13|1987-06-19|Lentia Gmbh|NEW CRYSTALLINE SALTS OF ARYLOXY PROPANOLAMINES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE|
    JPH0434989B2|1986-08-06|1992-06-09|Nippon Kayaku Kk|
    DE3706585A1|1987-02-25|1988-09-08|Schering Ag|ARYL- AND ARYLOXY-SUBSTITUTED TERT.-ALKYLENAMINE, METHOD FOR THE PRODUCTION THEREOF AND THEIR PHARMACEUTICAL USE|
    GB8925032D0|1989-11-06|1989-12-28|Ici Plc|Chemical compounds|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    SE7807408A|SE7807408L|1978-06-30|1978-06-30|HEART ACTIVE ASSOCIATIONS|
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