Patent DE-10039610-A1 (DE)
Title: Azepinoindole derivatives are PARP inhibitors and are useful for the treatment of neurodegenerative diseases, ischemia, tumor, septic shock, inflammation, rheumatic diseases, ARDS and diabetes mellitus
Inventor: LUBISCH WILFRIED
IPC: A61P35/00
Filed: 2000-08-09
Abstract: Azepinoindole derivatives are new.  The azepinoindole derivatives of formula (I) and their tautomers, enantiomers, diastereomers, salts and prodrugs are new:   A = 1-3C chain optionally substituted on each C by 1 or 2 1-4C alkyl, OH, 1-4C alkoxy, COOH, COO-1-4C alkyl or phenyl or optionally substituted with 1 oxo;  X<1>  = S, O, or NH; X<2>  = C optionally carrying a 1-4C chain; or N; X<3>  = N, or CR<2>; R<2>  = H, 1-6C alkyl, phenyl-1-4C alkyl, or phenyl; R<1>  = H, Cl, Br, I, 1-6C alkyl, OH, NO2, CF3, CN; NR<11>R<12>, NHCOR<13>, or 1-4C alkoxy; R<11>, R<12> = H or 1-4C alkyl; R<13> = H, 1-4C alkyl, phenyl-1-4C alkyl, or phenyl; B = an unsaturated, saturated or partly unsaturated mono-, bi- or tricyclic ring with up to 15C which (a) optionally contains up to 5 N atoms or 1 or 2 O or S atoms when it has up to 14C, (b) is substituted with 1 R<4> and up to 3 R<5>; and (c) is optionally substituted with =O on 1 or 2 C or S atoms; R<4>  = -(D)p-(E)s-(F<1>)q-G<1>-(F<2>)r-(G<2>)-G<3>; G<1>  = a bond or an unsaturated, saturated or partly unsaturated mono-, bi- or tricyclic ring with up to 15C which (a) optionally contains up to 5 N atoms or 1 or 2 O or S atoms when it has up to 14C, (b) is substituted with up to 3 R<5>; and (c) is optionally substituted with =O on 1 or 2 C or S atoms; G<2>  = NR<41>R<42>, a bond; or pyrrolidin-1-yl, piperidin-1-yl, 1,2,5,6-tetrahydropyridin-1-yl, 4-R<9>-piperazin-1-yl, 4-R<9>-1,4-diazepin-1-yl, azepin-1-yl or morpholin-1-yl (each ring-substituted with R<7>); G<3>  = H; or an unsaturated, saturated or partly unsaturated mono-, bi- or tricyclic ring with up to 15C which (a) optionally contains up to 5 N atoms or 1 or 2 O or S atoms when it has up to 14C, (b) is substituted with up to 3 R<5>; and (c) is optionally substituted with =O on 1 or 2 C or S atoms;  D  = S, NR<43>, or O; E  = phenyl, -C(O)-, -SO2-, -SO2NH-, -NHCO-, -CONH-, -NHSO2-, or -NHCOCH2X<4>-; X<4>  = S, O, or NH; F<1>, F<2>  = saturated or unsaturated 1-8C chain; p, q, r and s  = 0 or 1; R<41>  = H, 1-6C alkyl optionally substituted on each C with 1 or 2R<6>, phenyl optionally substituted with 1 or 2 R <6>, or (CH2)t-K; R<42> = H, 1-6C alkyl, COR<8>, CO2R<8>, SO2NH2, SO2R8, -(C=N)-R<8>, or -(C=N)-NHR<8>; R<43> = H or 1-4C alkyl; t  = 1-4; K  = NR<11>R<12>, NR<11>-(1-4C alkyl)-phenyl, pyrrolidinyl, piperidinyl, 1,2,5,6-tetrahydropyridinyl, morpholinyl, homopiperidinyl, or piperazinyl or homopipearzinyl (each optionally substituted with 1 1-6C alkyl);  R<5>  = H, Cl, F, Br, I, OH, NO2, CF3, CN; NR<11>R<12>, NHCOR<13>, (1-4C alkyl)-CONHR<13>, COR<8>, (0-4C alkyl)-OCOR<13>, phenyl-1-4C alkyl; phenyl, CO2-1-4C alkyl, or saturated or unsaturated 1-6C alkyl, 1-4C alkoxy or 1-4C alkylthio (each optionally substituted with 1 or 2 R<6>); R<6>  = H, Cl, F, Br, I, 1-6C alkyl, OH, NO2, CF3, CN, NR<11>R<12>, NHCOR<13>, or 1-4C alkoxy; R<7>  = H, 1-6C alkyl, phenyl optionally substituted with 1-3 Q, NR<11>R<12>, or a saturated 3-7 membered cyclic amino group or homopiperazinyl (each optionally substituted with 1 1-6C alkyl); Q = OH, 1-6C alkyl, 1-4C alkoxy, Cl, Br, I, F, CF3, NO2, or NH2; R<8>  = 1-6C alkyl, CF3, phenyl, or phenyl-1-4C alkyl optionally substituted with 1 or 2 Q; R<9>  = H, 1-6C alkyl, Ph-1-4C alkyl, CO2-(1-4C alkyl)-Ph, CO2-1-4C alkyl, SO2-Ph, COR<8>, or Ph; Ph  = phenyl optionally substituted 1 or 2 Q; compounds are excluded when: (a) X<2> = X<3> = N; (b) G<1> = G<2> = G<3> = H or a bond; and (c) two of G<1>-G<3> = H or a bond when p = s = 0 and q or r = 1 or p. q and r = 0.