Patent GB-1089071-A (GB)
Title: Indole derivatives
IPC: C07D209/18
Filed: 1965-02-08
Abstract: Novel indole compounds of the Formula I, <FORM:1089071/C2/1> <FORM:1089071/C2/2> wherein R1 is hydrogen, C1- 5 alkyl, C2- 5 alkenyl, C2- 5 alkynyl, ar-(C1- 5 alkyl), halo(C1- 5 alkyl), dihalo(C1- 5 alkyl), C1- 6 alkanoyl, C2- 6 alkenoyl, C2- 6 alkynoyl, aroyl, ar-(C1- 6 alkanoyl) or halo(C1- 6 alkanoyl); R2 is C2- 5 alkenyl or C1- 5 alkyl; R4 is hydrogen, fluorine, C1- 5 alkyl, C1- 5 alkoxy or trifluoromethyl; R5 is hydroxy, C1- 5 alkyl, C1- 5 alkoxy, nitro, amino, C1- 5 alkylamino, di(C1- 5 alky)amino, bis(hydroxy-C1- 5 alkyl)amino, 1-pyrrolidino, 4-methyl-1-piperazinyl, 4-morpholinyl, cyano, trifluoromethyl, halogen, di(C1- 5 alkyl) sulphamyl, benzythio, C1- 5 alkylbenzylthio, C1- 5 alkoxybenzylthio, halobenzylthio, benzyloxy, C1- 5 alkylbenzyloxy, C1- 5 alkoxybenzyloxy, halobenzyloxy, C2- 5 alkenyl, C2- 5 alkenyloxy, 1-azacyclopropyl, cyclopropylmethoxy or cyclobutylmethoxy, R6 is a carbocyclic or heterocyclic aromatic radical of one or two fused rings having 5 or 6 atoms to the ring, the possible hetero atoms being O, N or S and being confined to one ring and not exceeding 3 in number and in which the aromatic radical bears at least one halogen, C1- 5 alkyl, C1- 5 alkylthio, C1- 5 alkoxy, trifluoromethyl, phenoxy, C1- 5 alkylphenoxy, C1- 5 alkoxyphenoxy, halophenoxy, di(C1- 5 alkyl) sulphamoyl, cyano, trifluoromethylthio, C1- 5 alkylsulphinyl, C1- 5 alkylsulphonyl, benzylthio, (C1- 5 alkyl) benzylthio, (C1- 5 alkoxy) benzylthio, halobenzylthio, mercapto, nitro, amino, di(C1- 5 alkyl) amino, C1- 5 alkylamino, hydroxy, benzyloxy, C1- 5 alkylbenzyloxy, C1- 5 alkoxy-benzyloxy or halobenzyloxy substituents and M is a hydroxy, amino, C1- 5 alkylamino, di(C1- 5 alkyl)-amino, ar-(C1- 5 alkyl) amino, glycosylamino, allylamino, phenethylamino, N-ethyl-phenethylamino, p-chloroanilino, 1 - ethyl - 2 - aminomethyl - piperidino, tetrahydrofurfurylamino, 1,2,5,6-tetrahydropyridine, anilino, p-ethoxyanilino, cyclohexylamino, pyrrolidino, N-hydroxyethyl-piperazino, N,N-dimethylcarboxamidomethylamino, N,N - diethylaminoethylamino, armethoxy, C1- 5 alkoxy or OZ or OY radical wherein Z is a cation and Y is a second acyl radical derived from I by removing the group M; are made by reducing the corresponding glyoxalate or glyoxalamide of the Formula II with an alkali-metal borohydride, hydrogen in the presence of a hydrogenation catalyst, zinc amalgam or aluminium amalgam and, if desired, converting the resulting a -hydroxy compound into the a -alkoxy derivative by treatment with an aliphatic halide and silver oxide, or into an a -acyloxy derivative by acylating with an acid chloride or anhydride. Free acids of the Formula I (M=OH) may be prepared by pyrolysis of a corresponding t.-lower alkyl ester or reduction of an arylmethyl ester.  The free acids may be converted into amides or may be reacted with dicyclohexylcarbodiimide to give the corresponding anhydrides. Indolyl-3-glyoxalic compounds of the Formula II are made by reacting the appropriate 3-unsubstituted indole with glyoxalyl chloride and reacting the resulting indolyl-3-glyoxalyl chloride with an alcohol, amine, inorganic base or ammonia and, if required, with an acylating agent to introduce the group R6CO-.  Pharmaceutical preparations having anti-inflammatory, anti-pyretic and analgesic activity comprise the above compounds of the invention and an inert diluent, carrier or coating, suitably in the form of a pill, tablet, capsule lozenge, elixir, syrup or injectable or orally administrable solution or suspension.