1
We claim:
1, A compound of the formula I
<IMG>
in which
A can be a C1-C3 chain, where each carbon atom can
additionally carry one or two of the following
substituents: C1-C4-alkyl, OH, O-C1-C4-alkyl, COOH,
COO-C1-C4-alkyl and phenyl or a C atom can also carry an
=O group and
X1 can be S, O or NH and
X2 can be a carbon atom which can additionally carry a C1-C4
chain, and N and
X3 can be N or C-R2, where
R2 can be hydrogen, branched or unbranched C1-C6-alkyl,
C1-C4-alkylphenyl, phenyl and
X2 and X3 cannot simultaneously be N, and
R1 can be hydrogen, chlorine, fluorine, bromine, iodine,
branched or unbranched C1-C6-alkyl, OH, nitro, CF3, CN,
NR11R12, NH-CO-R13, O-C1-C4-alkyl, where R11 and R12
independently of one another are hydrogen or C1-C4-alkyl
and R13 is hydrogen, C1-C4-alkyl, C1-C4-alkylphenyl or
phenyl, and
B can be an unsaturated, saturated or partially unsaturated
mono-, bi- or tricyclic ring having at most 15 carbon
atoms, an unsaturated, saturated or partially unsaturated
mono-, bi- or tricyclic ring having at most 14 carbon
atoms and 0 to 5 nitrogen atoms, 0 to 2 oxygen atoms and
0 to 2 sulfur atoms, which in each case are additionally
substituted by one R4 and at most 3 different or
2
identical radicals R5, and can carry one or two carbon or
sulfur atoms and also one or two =O groups,
R4 is -(D)p-(E)s-(F1)q-G1-(F2)r-(G2)-G3. where G1, G2 and G3
cannot simultaneously be hydrogen or a bond and if p = s
= 0 and q or r = 1 or p, q and r = 0, then two radicals
G1, G2 and G3 cannot simultaneously be a bond or
hydrogen, and
D can be S, NR43 or O
E can be phenyl,
<IMG>, -SO2-, -SO2NH-, -NHCO-, -CONH-, NHSO2-,
-NHCOCH2X4,
and
X4 can be S, O or NH, and
F1 can be a straight-chain or branched saturated or
unsaturated carbon chain of 1 to 8 C atoms and
F2 independently of F1 has the same meaning as F1,
G1 is a bond or can be an unsaturated, saturated or
partially unsaturated mono-, bi- or tricyclic ring
having at most 15 carbon atoms, an unsaturated,
saturated or partially unsaturated mono-, bi- or
tricyclic ring having at most 14 carbon atoms and 0
to 5 nitrogen atoms, 0 to 2 oxygen atoms and 0 to 2
sulfur atoms, which in each case are additionally
substituted by at most 3 different or identical
radicals R5 and can carry one or two carbon or sulfur
atoms and one or two =O groups, and
G2 is NR41R42 or
<IMGS>
3
or a bond and
G3 can be an unsaturated, saturated or partially
unsaturated mono-, bi- or tricyclic ring having at
most 15 carbon atoms, an unsaturated, saturated or
partially unsaturated mono-, bi- or tricyclic ring
having at most 14 carbon atoms and 0 to 5 nitrogen
atoms, 0 to 2 oxygen atoms or 0 to 2 sulfur atoms,
which in each case are additionally substituted by at
most 3 different or identical radicals R5, and one or
two carbon or sulfur atoms can also carry one or two
=O groups, or hydrogen, and
p can be 0 or 1 and
s can be 0 or 1 and
q can be 0 or 1 and
r can be 0 or 1 and
R41 can be hydrogen, C1-C6-alkyl, where each carbon atom can
additionally carry up to two radicals R6, phenyl which
can additionally carry at most two radicals R6, and
(CH2)t-K and
R42 can be hydrogen, C1-C6-alkyl, -CO-R8, CO2-R8, SO2NH2,
SO2-R8, -(C=N)-R8 and -(C=N)-NHR8 and
R43 can be hydrogen or C1-C4-alkyl and
t can be 1, 2, 3 or 4 and
K can be NR11R12, NR11-C1-C4-alkylphenyl, pyrrolidine,
piperidine, 1,2,5,6-tetrahydropyridine, morpholine,
homopiperidine, piperazine, which can additionally be
substituted by an alkyl radical C1-C6-alkyl, and
homopiperazine which can additionally be substituted by
an alkyl radical C1-C6-alkyl, and
R5 can be hydrogen, chlorine, fluorine, bromine, iodine, OH,
nitro, CF3, CN, NR11R12, NH-CO-R13, C1-C4-alkyl-CO-NH-R13,
COR8, Co-C4-alkyl-O-CO-R13, C1-C4-alkylphenyl, phenyl,
CO2-C1-C4-alkyl, and branched or unbranched C1-C6-alkyl,
O-C1-C4-alkyl, S-C1-C4-alkyl, where each C atom of the
4
alkyl chains can carry up to two radicals R6 and the
alkyl chains can also be unsaturated, and
R6 can be hydrogen, chlorine, fluorine, bromine, iodine,
branched or unbranched C1-C6-alkyl, OH, nitro, CF3, CN,
NR11R12, NH-CO-R13, O-C1-C4-alkyl
R7 can be hydrogen, C1-C6-alkyl, phenyl, where the ring can
additionally be substituted by up to two radicals R71,
and one amine NR11R12 or a cyclic saturated amine having
3 to 7 members, which can additionally be substituted by
an alkyl radical C1-C6-alkyl, and homopiperazine which
can additionally be substituted by an alkyl radical
C1-C6-alkyl, and
where the radicals R11, R12 and R13 in K, R5, R6 and R7
independently of one another can assume the same meaning as
R1, and
R71 can be OH, C1-C6-alkyl, O-C1-C4-alkyl, chlorine, bromine,
iodine, fluorine, CF3, nitro, NH2, and
R8 can be C1-C6-alkyl, CF3, phenyl, C1-C4-alkylphenyl, where
the ring can additionally be substituted by up to two
radicals R81, and
R81 can be OH, C1-C6-alkyl, O-C1-C4-alkyl, chlorine, bromine,
iodine, fluorine, CF3, nitro, NH2, and
R9 can be hydrogen, C1-C6-alkyl, C1-C4-alkylphenyl,
CO2-C1-C4-alkylphenyl, CO2-C1-C4-alkyl, SO2-phenyl, COR8
and phenyl, where the phenyl rings can additionally be
substituted by up to two radicals R91, and
R91 can be OH, C1-C6-alkyl, O-C1-C4-alkyl, chlorine, bromine,
iodine, fluorine, CF3, nitro, NH2,
or its tautomeric forms, possible enantiomeric and
diastereomeric forms, and its prodrugs.
5
2. A compound of the formula I as claimed in claim 1, where
A is a C2 chain which can be substituted, and
X1 is 0 and
R1 is hydrogen.
3. A compound of the formula I as claimed in one of claims 1 and
2, in which
B can be an unsaturated, saturated or partially unsaturated
mono-, bi- or tricyclic ring having at most 15 carbon
atoms, an unsaturated, saturated or partially unsaturated
mono-, bi- or tricyclic ring having at most 14 carbon
atoms and 0 to 5 nitrogen atoms, 0 to 2 oxygen atoms or 0
to 2 sulfur atoms, which in each case are additionally
substituted by an R4 and at most 3 different or identical
radicals R5, and can carry one or two carbon or sulfur
atoms and also one or two =O groups.
4. A compound of the formula I as claimed in claim 3, where
B is phenyl, cyclohexyl, piperidine, pyridine, pyrimidine,
pyrrole, pyrazole, thiophene, furan, oxazole,
naphthalene, piperazine, quinoline, pyrazine, which can
additionally be substituted by one R4 or at most 2 R5.
5. A compound of the formula I as claimed in claim 4, where
R4 is D-F1 0,1-G2-G3 where G3 is hydrogen and
D is O or NR43, where R43 is hydrogen or C1-C3-alkyl and
F1 is C2-C4-alkyl.
6. A pharmaceutical comprising, in addition to customary
carriers and excipients, compounds of the formula I as
claimed in one of claims 1 to 5.
7. The use of compounds of the general formula I as claimed in
one of claims 1 to 5 for the production of pharmaceuticals
having PARP-inhibitory action.
6
8. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment of
neurodegenerative diseases and neuronal damage.
9. The use as claimed in claim 7 for the treatment of those
neurodegenerative diseases and that neuronal damage which
are/is caused by ischemia, trauma or mass hemorrhages.
10. The use as claimed in claim 7 for the treatment of stroke and
of craniocerebral trauma.
11. The use as claimed in claim 7 for the treatment of
Alzheimer's disease, Parkinson's disease and Huntington's
disease.
12. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment or
prophylaxis of damage due to ischemias.
13. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment of
epilepsy, in particular of generalized epileptic attacks,
such as, for example, petit mal and tonic/clonic attacks and
partially epileptic attacks, such as temporal lobe and
complex/partial attacks.
14. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment of
damage to the kidneys after renal ischemia, damage which is
caused by medicinal therapy, such as during cyclosporin
therapy, and for treatment during and after kidney
transplantation.
15. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment of
damage to the heart after cardiac ischemia.
16. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment of
microinfarcts such as during and after heart valve
replacement, aneurysm resection and heart transplantation.
17. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for treatment during
revascularization of critically constricted coronary arteries
7
such as in PTCA and bypass operations or critically
constricted peripheral arteries, in particular leg arteries.
18. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment of
acute myocardial infarct and of damage during and after its
medicinal or mechanical lysis.
19. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment of
tumors and metastases thereof.
20. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment of
multiorgan failure sepsis such as during septic shock and
acute respiratory distress syndrome.
21. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment of
immunological diseases such as inflammation and rheumatic
disorders, such as rheumatoid arthritis.
22. The use of compounds of the formula I as claimed in claim 7
for the production of pharmaceuticals for the treatment of
diabetes mellitus.
