IE34326B1 - Phenylaminoethanol derivatives - Google Patents

Abstract

1,266,058. Salicylamide derivatives. ALLEN & HANBURY'S Ltd. 29 June, 1970 [8 July, 1969], No. 34379/69. Addition to 1,200,886. Heading C2C. Novel salicylamide derivatives of the Formula VI: in which R<SP>2</SP> is an arylalkyl group, the alkyl portion of which contains 1 to 6 carbon atoms and the aryl portion of which may be substituted by one or more alkoxy or hydroxy radicals, or an aryloxyalkyl group, the alkyl portion of which contains from 1 to 6 carbon atoms, and the aryloxy portion of which is substituted by one or more alkoxy or hydroxy radicals, R<SP>3</SP> is H and X is CONH 2 , and physiologically acceptable acid addition salts thereof are prepared by (1) reducing compounds of Formula V: in which X is CONH 2 or a group convertible thereto, B<SP>2</SP> is H, benzyl or as defined above, and R<SP>3</SP> is H or benzyl, in which the phenolic hydroxy group may be protected to convert the CO group to CHOH, if necessary with subsequent conversion of X to CONH 2 and R<SP>2</SP> and R<SP>3</SP> to arylalkyl or aryloxyalkyl and hydrogen, respectively, and subsequent removal of any protective groups; (2) reacting compounds of Formula VI above in which X is CONH 2 and R<SP>2</SP> and R<SP>3</SP> are both H with the appropriate aldehydes or ketones and reducing the resulting azomethines; (3) reductively alkylating compounds of Formula VI in which X is CONH 2 and RQ and R<SP>3</SP> are both benzyl with the appropriate carbon compounds; and (4) reducing the azomethines obtained by reacting the appropriate glyoxals with amine of the formula R<SP>2</SP>NH 2 . 5 - [1 - Hydroxy - 2 - (1 - methyl - 3 - phenylpropylamino)-ethyl]salicylamide hydrochloride is separated into two racemic modifications by treatment with benzoic acid, separating and then hydrolysing the resulting benzoates. 5 - [N - Benzyl - N - (1 - methyl - 3 - phenylpropyl) - glycyl] salicylamide hydrochloride is obtained by reacting 5-bromoacetylsalicylamide with N benzyl - N - (1 - methyl - 3 - phenylpropyl) amine. 5 - (2 - Amino - 1 - hydroxyethyl) salwylamide hydrochloride is obtained by treating 5-(2-amino- 1-hydroxyethyl) salicylic acid methyl ester hydrochloride with ammonium hydroxide. 5 - [1 - Hydroxy - 2 - (1,1 - dimethyl - 3 - phenylpropylamino)ethyl]aalicylic acid methyl ester hydrochloride is made by hydrogenating the imine resulting from the reaction between 5- glyoxyloyl-salicylic acid methyl ester hydrate and 1,1-dimethyl-3-phenylpropylamine. Pharmaceutical compositions, having the ability to block both α- and #-adrenergic receptors and suitable for oral, rectal or parenteral administration, contain the above novel compounds or pharmaceutically acceptable acid addition salts and non-toxic carriers. [GB1266058A]