1350413 Benzotriazepine derivatives ROUSSEL-UCLAF 19 July 1971 [17 July 1970] 33735/71 Heading C2C The invention comprises novel benzotriazepines of the Formula I wherein M is H, C 1-6 alkyl, C 3-7 cycloalkyl, or aralkyl or aryl optionally substituted on the aromatic nucleus by halogen alkoxy or alkyl; MSP1/SP and MSP11/SP each are H, OH, NO 2 , C 1-6 alkoxy, CF 3 , or carboxy esterified with an aliphatic alcohol with up to 3 C atoms; A is S or = NH; when A is S, B is NH 2 ; when A is =NH, B is NH(OH), -NH(O-alkyl), (the alkyl having up to 5 C atoms and optionally substituted by alkoxycarbonyl or dialkylamino); NH(OCO hydrocarbyl), (the hydrocarbyl group being saturated or unsaturated and having up to 5 C atoms), NH(OCO phenyl), NH(OCO alkylene COOH) (the alkylene group having up to 5 C atoms), C 1-5 alkoxy, NRaRb, wherein Ra and Rb each are C 1-5 alkyl or optionally substituted aralkyl, or -NH(CH 2 )pNRcRd, wherein p is 1 to 7, and Rc and Rd each are C 1-5 alkyl or optionally substituted aralkyl, or B together with A and the intermediate carbon atom forms a heterocyclic radical selected from 2-imidazolin- 2-yl, 2-thiazolyl optionally substituted at the 4-position by C 1-5 alkyl, and 1,2,4-oxadiazol- 3-yl substituted at the S-position by a saturated or unsaturated hydrocarbyl group having up to 5 carbon atoms, phenyl, or C 1-5 alkylene -COOH, pharmaceutical acceptable acid addition salts, and the preparation thereof. The above compounds are obtained by one of the following methods: (a) compounds of the above Formula I in which B is NH(OH), NH(OCO hydrocarbyl), NH (OCO phenyl), or NH (OCO alkylene COOH) by reacting cyano compounds of the Formula X with hydroxylamine or acid addition salts thereof, followed by, if desired, acylation; (b) compounds in which C(=A)B is a 1,2,4-oxadiazol- 3-yl radical substituted in the 5-position by hydrocarbyl, phenyl or alkylene -COOH by heating the corresponding compounds in which B is NH (OCO hydrocarbyl), NH (OCO phenyl), or NH (OCO alkylene COOH); (c) compounds in which A is S and B is NH 2 by reacting compounds of the above Formula X with H 2 S in the presence of a strong base; (d) compounds in which C (=A)B is 2-thiazolyl radical optionally substituted in the 4-position by an alkyl group by reacting compounds of Formula I above in which A is S and B is NH2 with compounds of the formula CH 2 ClCORg, wherein R 7 is H or alkyl; (e) compounds in which B is alkoxy optionally substituted by an acyloxy group derived from a monocarboxylic or free or salified dicarboxylic organic acid by reacting compounds of Formula X with the appropriate alkanols; and (f) compounds in which B is NRaRb, NH(CH 2 )p RcRd or NHOAlkyl, or in which C(=A)B is 2-imidazolin-2-yl by reacting compounds of Formula I in which B is alkoxy with compounds of the formula H 2 NRaRb, H2N(ZH 2 )pNRcRd; H 2 NOAlkyl and ethylenediamine respectively. Cyano compounds of the above Formula X are obtained by cyclizing the appropriate N-(m)-N- cyanoacetyl - o - phenylenediamines, resulting from the reduction of the corresponding N-(m)- N - cyanoacetyl - o - nitroanilines, which are made by reacting N-(m)-o-nitroanilines with cyanoacetic acid in the presence of phosphorus pentachloride. Pharmaceutical compositions, suitable for oral, perlingual or transcutaneous administration, contain the above novel benzotriazepines or pharmaceutically acceptable acid addition salts thereof in association with suitable vehicles. The compounds possess thymo-analeptic and antidepressant activities.
展开▼
