Patent GB-1259648-A (GB)
IPC: A61K8/00
Filed: 1969-02-28
Abstract: 1,259,648. Dibenzazepine derivatives. J. R. GEIGY A.G. 28 Feb., 1969 [29 Feb., 1968], No. 10697/69. Heading C2C. Novel dibenzazepine derivatives of Formula (I) in which R 1  is hydrogen or C 1-3  alkyl, R 2  is hydrogen or C 1-4  alkyl and R 3  is hydrogen or chlorine, and their pharmaceutically acceptable salts with bases, are prepared by (a) subjecting a compound of Formula (II) in which R 2 <SP>1</SP> is hydrogen, C 1-4  alkyl, C 1-4  alkanoyl or benzyl, to alcoholysis with a C 1-6  alkanol and hydrolysing the resulting alkyl ester, or (b) hydrolysing a compound of Formula (III) in which R 2 <SP>11</SP> is hydrogen, C 1-4  alkyl or C 1-4  alkanoyl, and X is a group which can be hydrolysed to obtain a carboxyl group, e.g. a cyano, carboxylic acid imido ester, carboxylic acid ester or carbamoyl group, or a thiocarbamoyl group which can be mono- or di-alkyl substituted at the N-atom, whereby in the case of di-substitution, the two alkyl groups may be joined by way of an oxygen atom, or (c) hydrolysing a compound of Formula (IV) in which R 2 <SP>111</SP> is C 1-4  alkanoyl, or (d) reacting a compound of Formula (V) in which R 4 <SP>1</SP> is hydrogen, C 1-6  alkyl or benzyl, with a saturated solution of a hydrohalic acid at an elevated temperature, or (e) reacting a compound of Formula (V) in which R 4 <SP>1</SP> is benzyl, with catalytically activated hydrogen, or (f) reacting a compound of Formula (VI) with a reactive ester of a C 1-4  alkanol, or (g) reacting a compound of Formula (VII) in which R 1 <SP>1</SP> is C 1-3  alkyl, A 1  is cyano or C 2-6  (alkoxycarbonyl) and A 2  is C 2-6  (alkoxycarbonyl), C 3-7  (alkoxalyl), cyano or acetyl, with an alkali metal hydroxide in an organic or organic-aqueous medium or, if neither A 1  nor A 2  is cyano, also with an alkali metal alkanolate in an anhydrous medium or, if A 2  is not acetyl, also with a mineral acid in an organic-aqueous medium, and optionally in any of processes (a) to (g) liberating the carboxylic acid from a salt obtained and/or converting the obtained carboxylic acid into a pharmaceutically acceptable salt with a base. Intermediates and starting materials.-The following 10,11-dihydro-5H-dibenz[b,f]azepine compounds are prepared in the examples: 3- cyanomethyl - 5 - methyl -, 3- cyanomethyl- 5 - butyl -, 3 - (1 - cyanoethyl) - 5 - methyl-, 2 - cyanomethyl - 5 - benzyl -, 2 - cyanomethyl- 5 - methyl -, 2 - cyanomethyl - 5 - methyl- 7 - chloro -, 2 - cyano - 5 - methyl -, 3 - ethoxycarbonylmethyl - 5 - methyl -, 3 - (1 - ethoxycarbonyl - ethyl) - 5 - methyl -, 2 - ethoxycarbonylmethyl -, 3 - methoxycarbonyl -, 3 - (1 - methoxycarbonyl - ethyl) -, 3 - methoxycarbonylmethyl - 5 - methyl -, 3 - methoxycarbonylmethyl - 5 - butyl -, 2 - ethoxycarbonylmethyl - 5 - methyl -, 2 - (1 - ethoxycarbonyl - propyl) - 5 - methyl -, 2 - di - (ethoxycarbonyl)methyl -, 2 - [1,1 - di - (ethoxycarbonyl)ethyl] -, 2 - [1,1 - di - (ethoxycarbonyl)- propyl] -, 3 - carboxy - 5 - butyryl -, 3 - carboxy - 5 - acetyl -, 3 - (1 - carboxyethyl) - 5 - acetyl -, 3 - (1 - hydroxyethyl) - 5 - acetyl -, 3 - hydroxymethyl - 5 - acetyl -, 3 - hydroxymethyl - 5 - methyl -, 3 - hydroxymethyl - 5 - butyl -, 3 - (1 - hydroxyethyl) - 5 - methyl -, 2- hydroxymethyl - 5 - methyl -, 3 - hydroxymethyl - 5 - benzyl -, 3 - acetyl - 5 - butyryl-, 3 - acetyl - 5 - methyl -, 2 - acetyl - 5 - methyl-, 5 - benzyl -, 5 methyl-, 2 - formyl - 5 - methyl-, 2 - formyl - 5 - benzyl -, 3 - acetyl - 5 - formyl-, 3 - (1 - hydroxyethyl) - 5 - formyl -, 3 - carboxy- 5 - formyl -, 3 - methoxycarbonylmethyl - 5 - formyl -, 3 - (1 - methoxycarbonyl - ethyl)- 5 - formyl -, 2 - carbamoyl - 5 - methyl -, 3- carboxy - 5 - acetyl - 7 - chloro -, 3,5 - diacetyl- 7 - chloro -, 3 - hydroxymethyl - 5 - acetyl - 7 - chloro -, 3 - methoxycarbonyl - 5 - acetyl - 7 - chloro -, 3 - carboxymethyl - 5 - acetyl - 7 -  chloro -, 2 - carboxymethyl - 5 - benzyl -, 3- methoxycarbonylmethyl - 5 - methyl -, 3,5- diacetyl - 7 - chloro -, 3 - chloro - 5 - acetyl-, 3 - bromomethyl - 5 - acetyl -, 3- (1 - bromoethyl) - 5 - acetyl -, 2 - hydroxymethyl - 3- chloro - 5 - methyl -, 2 - hydroxymethyl - 5 - methyl - 7 - chloro -, 2 - formyl - 3 - chloro - 5 - methyl -, 2 - formyl - 5 - methyl - 7 - chloro -, 2 - hydroxyliminomethyl - 5 - methyl -, 3 - (2- imino - 2 - ethoxy - 1 - ethyl) - 5 - methyl -, 3- bromomethyl - 5 - methyl -, 3 - bromomethyl- 5 - butyl -, 3- (1 - bromoethyl) - 5 - methyl-, 2 - bromomethyl - 5 - benzyl -, 2 - chloromethyl - 5 - benzyl -, 2 - chloromethyl - 5 - methyl -, 2 - chloromethyl - 5 - methyl - 7 chloro -, 3 - chloro - 5 - methyl-, 2 - or 3 -  morpholinothiocarbonylmethyl - 5 - methyl -, 3 - morpholinothiocarbonylmethyl - 5 - acetyl-, 3 - cyanomethyl - 5 - acetyl -, 3- cyanomethyl- 5 - acetyl - 7 - chloro - and 3 - (1 - cyanoethyl). 5 - acetyl - 10,11 - dihydro - 5H - dibenz[b,f]- azepines. Pharmaceutical compositions having antiinflammatory, anti-oedematous, analgesic and anti-pyretic activity comprise, as active ingredient, one of the above novel compounds or salts, together with a pharmaceutical carrier. The compositions may be administered orally, parenterally, rectally or topically. The active compounds are also UV-absorbers and can be used in sun-protection oils and creams.