Patent GB-1488978-A (GB)
Title: 4-aryl-1,2,3,4-tetrahydropyrrolo(3,4-b)indoles
IPC: A61K31/40
Filed: 1975-03-26
Abstract: 1488978 4 - Phenyl - 1,2,3,4 - tetrahydropyrrolo[3,4-b]indoles PFIZER Inc 26 March 1975 [1 April 1974] 12772/75 Heading C2C Novel 4 - phenyl - 1,2,3,4 - tetrahydropyrrolo- [3,4-b]indoles of the general Formula I wherein X is a hydrogen, fluorine, chlorine or bromine atom or a methyl group, Z is a hydrogen, fluorine or chlorine atom or a methoxy group and R is a hydrogen atom, a C 1-6  alkyl group, a benzyl group or a group of the Formula X wherein A is a C 1-5  alkylene group, M is in which R 1  is a hydrogen atom or C 2-6  alkanoyl group, and Y is a hydrogen, fluorine or chlorine atom or a methyl group, and pharmaceutically acceptable acid addition salts thereof are prepared (a) when R is a hydrogen atom, by heating a 2 - ethoxycarbonyl - 4 - phenyl - 1,2,3,4- tetrahydropyrrolo[3,4-b]indole of the general Formula III with KOH in ethanol; (b) when R is other than a hydrogen atom and M is -CH 2 - or -CO-, by reacting the corresponding compound in which R is a hydrogen atom with R-halogen; (c) when R is an alkyl group, by treating a 1,2,3,4 - tetrahydropyrrolo[3,4-b]indole of the general Formula IV with an appropriate bromobenzene in the presence of Cu 2 Br 2  and Na 2 CO 3 ; (d) when R is an alkyl group, by reducing the corresponding compound in which R is a R<SP>1</SP>-CO- group (R<SP>1</SP> being a C 1-5  alkyl group) with a metal hydride; (e) when R is a methyl group, by reducing the corresponding compound in which R is an ethoxycarbonyl group with LiAlH 4 ; (f) when R is a group of the Formula X, in which M is -CO-, by treating a cyanide of the general Formula VI with an appropriate Grignard reagent; (g) when R is a group of the Formula X and M is -CH(OH)-, by reducing the corresponding ketone with NaBH 4 ; (h) when R is a group of the Formula X and M is -C(OR 1 )(CH 3 ) and R 1  is H, by reacting the corresponding compound in which M is -CO- with CH 3 MgI; (i) when R is a group of the Formula X, M is -CH(OR 1 ) or -C(OR 1 )(CH 3 )- and R 1  is a C 2-6  alkanoyl group, by acylation of the corresponding compound in which R 1  is H, and (j) when R is a group of the Formula X and M is -CH = CH-, by dehydrating the corresponding compound in which M is -CH(OR 1 ); followed optionally by salification. 2 - Ethoxycarbonyl - 4 - phenyl - 1,2,3,4- tetrahydropyrrolo[3,4-b]indoles (III) are prepared by reacting an X-substituted phenylhydrazine with 1-ethoxycarbonyl-3-pyrrolidinone, cyclizing the resulting hydrazone with phosphoric acid and treating the resulting X- substituted 2 - ethoxycarbonyl - 1,2,3,4 - tetrahydropyrrolo[3,4-b]indole with an appropriate bromobenzene in the presence of Cu 2 Br 2  and Na 2 CO 3 . 2 - Alkanoyl - 4 - phenyl - 1,2,3,4 - tetrahydropyrrolo[3,4-b]indoles of the general Formula V are prepared by acylating the corresponding 2-unsubstituted compound. 1,2,3,4 - Tetrayhdropyrrolo[3,4-b]indoles (IV) are prepared by reacting an X-substituted phenylhydrazine with a 1-R-3-pyrrolidinone and cyclizing the resulting hydrazone with phosphoric acid. Pharmaceutical compositions having tranquillizing activity comprise, as active ingredient, a 4 - phenyl - 1,2,3,4 - tetrahydropyrrolo- [3,4-b]indole (I) wherein R is other than a hydrogen atom, or a pharmaceutically acceptable acid addition salt thereof, in admixture with a pharmacologically acceptable carrier, and may be administered orally or parenterally.