Patent DE-10022925-A1 (DE)
Title: New indole-carboxamide or azepino-indole derivatives and analogs, are poly-ADP ribose polymerase inhibitors useful e.g. for treating neurodegenerative disease, ischemia, epilepsy, tumors, sepsis or diabetes mellitus
Inventor: LUBISCH WILFRIED
IPC: A61K31/404
Filed: 2000-05-11
Abstract: Indole-4- or 7-carboxamide, -thiocarboxamide or -amidine derivatives (I) and (II) (including tricyclic analogs such as tetrahydroazepino-indolones) are new.  Indole-4- or 7-carboxamide, -thiocarboxamide or -amidine derivatives (I) and (II) (including tricyclic analogs such as tetrahydroazepino-indolones) of formulae (I) and (II) and their tautomers, enantiomers, diastereomers and prodrugs are new.   Q1 = H and Q2 = R3, or Q1 + Q2  = B (completing a fused ring); X = S, O or N; B = 1-3C chain, in which each C atom is optionally substituted by 1 or 2 of alkyl, OH, alkoxy, COOH, alkoxycarbonyl, phenyl or =O; R1 = H, halo, T, OH, CF3, CN, NR11R12 or NHCOR13; T = 1-6C alkyl; R11, R12 = H or alkyl; R13 = H, alkyl, alkylphenyl or phenyl; R2, R3 = H, T, alkylphenyl or phenyl and R3 may additionally = COOH, alkoxycarbonyl or CONH2 (where each C atom of the alkyl chains is optionally substituted by 1 or 2 of OH, alkoxy, NR11R12, COOH or alkoxycarbonyl); A = saturated or unsaturated, mono-, bi- or tricyclic ring system having upto 15C (e.g. phenyl, naphthalene, tetrahydronaphthalene, indane, fluorene, carbazole or cyclohexane) or a saturated, partially unsaturated or unsaturated, mono-, bi- or tricyclic ring system having upto 14C and 0-5 N, 0-2 O or 0-2 S (e.g. pyridine, thiophene, quinoline, quinoxaline, furan, imidazole, pyrrole, indole, benzimidazole, pyrimidine, pyrazine, benzofuran, benzothiophene, quinazoline or isoxazole), all optionally substituted by one R4 and/or 1-3 R5; R4 = H or -(D)p-E-(F')q-G; D = S, NR43 or O; E = phenylene or a direct bond; G = NR41R42, or pyrrolidino, piperidino, 1,2,3,6-tetrahydropyridin-1-yl, N-(R9)-piperazino, N-(R9)-homopiperazino, homopiperidino or morpholino (all monosubstituted by R7); F' = 1-8C carbon chain; p, q = 0 or 1; R41 = H, T, phenyl (optionally substituted by 1 or 2 R6) or -(CH2)rH'; R42 = H, T, COR8, SO2R8, -(C=N)-R8 or -(C=N)-NHR8; R43 = H or alkyl; r = 1-4; H' = NR11R12, N(R11)-alkyl-phenyl, pyrrolidine, piperidine, 1,2,3,6-tetrahydropyridine, piperazine (optionally substituted by T), homopiperazine (optionally substituted by T), homopiperidine or morpholine; R5, R6 = H, halo, T, OH, NO2, CF3, CN, NR11R12, NHCOR13 or alkoxy; R7 = H, T, phenyl (optionally substituted by 1 or 2 R71), NR11R12 or 3-7 membered saturated cyclic amine (e.g. pyrrolidine or piperidine); R71 = OH, T, alkoxy, halo, CF3, NO2 or NH2; R8, R9 = T, phenyl or alkylphenyl (where the ring is optionally further substituted by 1 or 2 R81); R81 = OH, T, alkoxy, halo, CF3, NO2 or NH2. Alkyl groups have 1-4C unless specified otherwise. The compounds 4-carboxamido-2-(1-ethylpiperidin-4-yl)-1H-indole and 4-carboxamido-2-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole are excluded. An Independent claim is claimed for the use of (I) or (II) for the preparation of a medicament for the treatment of neuronal disease and neuronal damage, where if Q1 = H and Q2 = R3, then A may additionally be H or T.