Heterocyclic compounds and their use as PARP inhibitors

1. Compound of the formula I

in which

A 1 is carboxamide, and

A 2 is hydrogen, and

X 1 is N or C—R 2 , and

X 2 is CH, and

R 2 is hydrogen, C 1 –C 6 -alkyl, C 1 –C 4 -alkyl-phenyl, or phenyl and

R 1 is hydrogen, and

B is optionally substituted thienyl, pyridinyl, indolyl, quinolinyl, isoquinolinyl, piperidinyl, cyclohexyl, naphthyl, quinoxalinyl, phenyl or phenyl further substituted with piperazinyl, piperidinyl or pyrolidinyl; each of which is optionally substituted by one R 4 and a maximum of three identical or different R 5 radicals, and

R 4 is hydrogen or -(D) p -(E) s -(F 1 ) q -G 1 -(F 2 ) r -(G 2 )-G 3 , where

D is S, NR 43 or O

E is -phenyl,

—SO 2 —, —SO 2 NH —, NHCO—, —CONH, or —NHSO 2 , and

s is 0 or 1 and

G 1 is a bond or an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring with a maximum of 15 carbon atoms, or an unsaturated, saturated or partially saturated mono-, bi- or tricyclic ring with a maximum of 14 carbon atoms and 0 to 5 nitrogen atoms, 0 to 2 oxygen atoms and 0 to 2 sulfur atoms, each of which is also substituted by a maximum of 3 different or identical R 5 radicals, and one or two carbon or sulfur atoms may also carry one or two ═O groups, and

G 2 is NR 41 R 42 ,

or a bond and

G 3 is an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring with a maximum of 15 carbon atoms, or an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring with a maximum of 14 carbon atoms and 0 to 5 nitrogen atoms, 0 to 2 oxygen atoms and 0 to 2 sulfur atoms, each of which is also substituted by a maximum of 3 different or identical R 5 radicals, and one or two carbon or sulfur atoms may also carry one or two ═O groups, or is hydrogen, and

p is 0 or 1 and

F 1 is a C 1 –C 8 -alkyl chain, and

F 2 independently of F 1 has the same meaning as F 1 ,

q is 0 or 1, and

r is 0 or 1 and

R 41 is hydrogen, C 1 –C 6 -alkyl, C 1 –C 6 -alkyl-phenyl, phenyl, it being possible for each carbon atom of the alkyl chains and the phenyl rings also to carry a maximum of two R 6 radicals, or (CH 2 ) t —K and

R 42 is hydrogen, C 1 –C 6 -alkyl, —CO 2 —R 8 , —CO—R 8 , —SO 2 —R 8 , —(C═NH)— R 8 or —(C═NH)—NHR 8 and

is hydrogen or C 1 –C 4 -alkyl and

t is 1, 2, 3, or 4 and

K is NR 11 R 12 , NR 11 —C 1 –C 4 -alkyl-phenyl, pyrrolidine, piperidine, 1,2,5,6-tetrahydropyridine, morpholine, homopiperidine, homopiperazine, or piperazine, each of which is optionally substituted by a C 1 –C 6 -alkyl radical or also by a C 1 –C 6 -alkyl-phenyl radical and the phenyl radical can also be substituted by a maximum of two R 81 ,

R 5 is hydrogen, chlorine, fluorine, bromine, iodine, C 1 –C 6 -alkyl, nitro, CF 3 , CN, NR 11 R 12 , NH—CO—R 13 , or O—C 1 –C 4 -alkyl, and

R 6 is hydrogen, chlorine, fluorine, bromine, iodine, C 1 –C 6 -alkyl, OH, nitro, CF 3, CN, NR 11 R 12 , NH—CO—R 13 , or O—C 1 –C 4 -alkyl, and

R 7 is hydrogen, C 1 –C 6 -alkyl, phenyl, optionally substituted by up to two identical or different R 71 radicals, or an amine NR 11 R 12 , or a cyclic saturated amine with 3 to 7 members, which may also be substituted by an alkyl radical C 1 –C 6 -alkyl, R 11 and R 12 are, independently of one another, hydrogen or C 1 –C 4 -alkyl, and R 13 is hydrogen, C 1 –C 4 -alkyl, C 1 –C 4 -alkyl-phenyl or phenyl, and

R 71 is OH, C 1 –C 6 -alkyl, O—C 1 –C 4 -alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro or NH 2 , and

R 8 is C 1 –C 6 -alkyl, CF 3 , phenyl or C 1 –C 4 -alkyl-phenyl, where the phenyl ring is optionally substituted by up to two R 81 radicals, and

R 81 is OH, C 1 –C 6 -alkyl, O—C 1 –C 4 -alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro or NH 2 , and

R 9 is hydrogen, C 1 –C 6 -alkyl, C 1 –C 4 -alkyl-phenyl, CO 2 —C 1 –C 4 -alkyl-phenyl, CO 2 —C 1 –C 4 -alkyl, —SO 2 -phenyl, —COR 8 or phenyl, where the phenyl rings are optionally substituted by up to two identical or different R 91 radicals, and

R 91 is OH, C 1 –C 6 -alkyl, O—C 1 –C 6 -alkyl, chlorine, bromine, iodine, fluorine, CF 3 , nitro or NH 2 ,

or the tautomeric forms, possible enantiomeric and diasteromeric forms thereof.

2. A compound of the formula I as claimed in claim 1 , where

B is phenyl, pyridine or piperidine, each of which may also be substituted by an R 4 and R 5 radical.

3. A compound of the formula I as claimed in claim 1 , where

R 4 is hydrogen or D 0,1 -F 1 0,1 -G 2 -G 3 where G 3 is hydrogen and G 2 is not a bond and

D is O or NR 43 , where R 43 is hydrogen or C 1 –C 3 -alkyl and

F 1 is C 2 –C 4 -alkyl.

4. A process for the treatment or prophylaxis of damage due to an ischemia, said process comprising administering an effective amount of a drug produced from the compound of claim 1 to a patient in need thereof.

5. A process for the treatment of damage to the heart after a cardiac ischemia, said process comprising administering an effective amount of a drug produced from the compound of claim 1 to a patient suffering from said damage.

6. A drug comprising a compound of claim 1 and a pharmaceutically acceptable carrier.