Patent GB-1437804-A (GB)
Title: Indole derivatives
IPC: C07D209/96
Filed: 1973-09-10
Abstract: 1437804 Indole derivatives GRUPPO LEPETIT SpA 22 Aug 1974 [10 Sept 1973] 42367/73 Heading C2C The invention comprises compounds having the general formula and its tautomeric forms wherein R is hydrogen or methoxy; R 1  is hydrogen, C 1  to C 4  alkyl, C 1  to C 4  alkyl substituted by carboxy, carbo (C 1  to C 4  alkoxy) or carbamyl, phenyl, benzyl, C 1  to C 4  aliphatic acyl, benzoyl or halobenzoyl; R 2  is hydrogen, C 1  to C 4  alkyl, carbo(C 1  to C 4 )- alkoxy, carbamyl, phenylcarbamyl, C 1  to C 4  aliphatic acyl, benzoyl or halobenzoyl; R 3  is halo, C 1  to C 4  alkyl, C 1  to C 4  alkyl substituted by carboxy, carbo(C 1  to C 4 )alkoxy, carbamyl, halo, amino, mono- or di-C 1  to C 4  alkylamino, phthalimido or morpholino, phenyl, phenyl substituted by C 1  to C 4  alkoxy, halo, nitro, amino or acetamido, and R 4  is hydrogen or C 1  to C 4  alkyl; with the proviso that when simultaneously, R 1  is hydrogen, methyl, phenyl, benzyl, acetyl or benzoyl, R 2  is hydrogen, C 1  to C 4  alkyl or acetyl, and R 3  is C 1  to C 4  alkyl or phenyl, R 4  must not be hydrogen or methyl; or R 3  and R 4  taken together with the adjacent carbon atom is a 5 or 6-membered alicyclic ring; and its pharmaceutically acceptable acid addition salts. They may be prepared by (a) heating at 10 to 150 C., in the presence of a condensing agent selected from POCl 3 , PCl 5 , PBr 3 , PCl 3 , triphenylphosphine/carbon tetrachloride mixtures and phosgene, a compound of the formula wherein R 1  is hydrogen, C 1  to C 4  alkyl optionally substituted with carbo(C 1  to C 4 )alkoxy, phenyl or benzyl; R is hydrogen or methoxy; R 2  is hydrogen or C 1  to C 4  alkyl; R 3  is halo, C 1  to C 4  alkyl optionally substituted with carbo(C 1  to C 4 )- alkoxy, halo, amino, mono- or di-C 1  to C 4  alkylamino, phthalimido or morpholino, phenyl optionally substituted with C 1  to C 4  alkoxy halo or nitro; R 4  is hydrogen or C 1  to C 4  alkyl with the proviso that when simultaneously, R 1  is methyl, phenyl or benzyl, R 2  is C 1  to C 4  alkyl, R 3  is C 1  to C 4  alkyl or phenyl, R 4  is not hydrogen or methyl; or R 3  and R 4  taken together with the adjacent carbon atom may represent a 5 or 6 memberedalicyclicringand (b)when in compound I R 1  is required to be (1) C 1  to C 4  aliphatic acyl, (2) benzoyl or (3) halobenzoyl reacting the compound obtained in step (a) wherein R 1  is hydrogen with (1) a C 1  to C 4  aliphatic acid, (2) benzoic acid or (3) halobenzoic acid, or the chloride or anhydride thereof; (c) when in I R 2  is required to be (1) carbo(C 1  to C 4  alkoxy), (2) C 1  to C 4  aliphatic acyl, (3) benzoyl, (4) halobenzoyl, (5) carbamyl, or (6) phenylcarbamyl, reacting a compound obtained by step (a) wherein R 2  is hydrogen with respectively, (1) a (C 1  to C 4  alkoxy) carbonyl chloride, (2) C 1-4  aliphatic acid or chloride or anhydride thereof, (3) benzoic acid, benzoyl chloride or benzoic acid anhydride, (4) halobenzoic acid or chloride or anhydride-thereof, (5) isocyanic acid or (6) phenyl isocyanate; (d) when in I R 1  and/or R 3  are required to be (1) carboxy(C 1  to C 4  alkyl), or (2) carbamyl(C 1  to C 4  alkyl), subjecting the compound obtained by step (a) wherein R 1  and/or R 3  is carbo(C 1  to C 4  alkoxy) C 1  to C 4  alkyl to, (1) alkaline hydrolysis or (2) reaction with ammonium hydroxide in a C 1  to Cl 4  alkano; (e) when in I R 3  is required to be phenyl substituted with amino, catalytically hydrogenating a compound obtained by step (a) in which R 3  is nitrophenyl; and (f) when in I R 3  is required to be acetamidophenyl, treating a compound obtained by step (e) with acetyl chloride or anhydride. The compounds of the invention exhibit antiinflammatory activity and may be administered orally, rectally or intramuscularly alone or with a pharmaceutically acceptable diluent or carrier.