Claims
- 1. A compound selected from the group consisting of2-(4-(N,N-2-(N,N-diethylamino)eth-1-ylmethylamino)phenyl)benzimidazole-4-carboxamide, 2-(4-(N,N-2-(N,N-dimethylamino)eth-1-ylmethylamino)phenyl)benzimidazole-4-carboxamide, and 2-(3-(2-(N,N-dimethylamino)eth-1-yl)-4-nitrophenyl)benzimidazole-4-carboxamide, or a prodrug or salt thereof.
- 2. A method of preparing a pharmaceutical composition for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase which comprises admixing an effective amount of a compound of formula I whereinA is N or CH, R1 is hydrogen or C1-C6-alkyl which optionally carries a radical OR11, R11 is hydrogen or C1-C4-alkyl, R2 is hydrogen, chlorine, fluorine, bromine, iodine, C1-C6-alkyl, nitro, CF3, CN, OR21, NR21R22 or NH—CO—R23, R21 and R22 are independent from one another and denote hydrogen or C1-C4-alkyl, R23 is hydrogen, C1-C4-alkyl or phenyl, R3 is NR31R32 or (CH2)q—NR33R34, q is 1, 2 or 3, R31 is hydrogen, C1-C6-alkyl or (CH2)rNR33R34, R32 is (CH2)rNR33R34, r is 2, 3, 4, 5 or 6, R33 and R34 are independent from one another and denote hydrogen, C1-C6-alkyl, together with the nitrogen to which they are bonded form a 3 to 8-membered ring formed of the nitrogen atom, carbon ring members and optionally one ring member selected from the group consisting of O, NH, N(C1-C4-alkyl) and N(C0-C2-alkylphenyl), phenyl-C1-C4-alkyl, wherein the phenyl ring is unsubstituted or substituted by 1 to 3 radicals selected from the group consisting of C1-C6-alkyl, halogen, nitro, SO2NR35R36, C1-C4-alkoxy, S(O)0-2—R37, CF3, (CH2)0-4—COR37, (CH2)0-4—NR35R36, (CH2)0-4—CONR35R36, (CH2)0-4—OR37, (CH2)0-4—CH2COOR37, R35 and R36 are independent from one another and denote hydrogen or C1-C4-alkyl, or R35 and R36 together with the nitrogen to which they are bonded form a 3 to 8-membered ring formed of the nitrogen atom, carbon ring members and optionally one ring member selected from the group consisting of O, S, SO2, NH, N(C1-C4-alkyl) and N(C0-C2-alkylphenyl), R37 is hydrogen or C1-C4-alkyl, R4 is hydrogen, C1-C6-alkyl, chlorine, bromine, fluorine, nitro, cyano, OR41, NR41R42 or NH—CO—R43, R41 and R42 are independent from one another and denote hydrogen or C1-C4-alkyl, and R43 is C1-C4-alkyl or phenyl, or a tautomeric form, an enantiomeric or diastereomeric form, or a prodrug or a physiologically tolerable salt thereof, with at least one customary pharmaceutical auxiliary.
- 3. The method of claim 2, wherein R2 is in the 3-position and R4 is in the 4-position, or R2 is in the 4-position and R3 is in the 3-position relative to the benzimidazole ring.
- 4. The method of claim 2, wherein R1 and R4 are hydrogen.
- 5. The method of claim 2, wherein R2 is hydrogen, nitro, CN, NH2, C1-C6-alkyl or O—C1-C4-alkyl.
- 6. The method of claim 2, wherein R3 is —CH2—NR33R34, —(CH2)2—NR33R34, —N(R31)—(CH2)2—NR33R34 or —N(R31)—(CH2)3—NR33R34, andR31 is hydrogen or C1-C4-alkyl, R33 and R34 are independent from one another and denote hydrogen or C1-C4-alkyl, or R33 and R34 together with the nitrogen to which they are bonded form a ring selected from the group consisting of piperidine, pyrrolidine, azepine and piperazine, wherein the second nitrogen ring member of the piperazine ring carries hydrogen or a C1-C4-alkyl group.
- 7. The method of claim 2, wherein R2 is hydrogen and A is nitrogen.
- 8. The method of claim 7, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase due to sepsis or multi-organ failure.
- 9. The method of claim 7, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase due to diabetes mellitus.
- 10. The method of claim 2, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase due to a neurodegenerative disease or neuronal damage.
- 11. The method of claim 10, wherein the neurodegenerative disease or neuronal damage is due to ischemia, trauma or mass hemorrhages.
- 12. The method of claim 10, wherein the neurodegenerative disease or neuronal damage is due to a stroke or a craniocerebral trauma.
- 13. The method of claim 10, wherein the neurodegenerative disease or neuronal damage is due to Alzheimer's disease, Parkinson's disease or Huntington's disease.
- 14. The method of claim 2, wherein the pharmaceutical composition is adapted for the treatment or prophylaxis of a pathologically increased activity of poly(ATP-ribose)polymerase due to ischemia.
- 15. The method of claim 2, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase due to epilepsy.
- 16. The method of claim 2, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase due to kidney damage, renal ischemia or kidney transplantation.
- 17. The method of claim 2, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase due to damage to the heart after cardiac ischemia.
- 18. The method of claim 2, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase due to a microinfract, a heart valve replacement, an aneurysm resection or a heart transplantation.
- 19. The method of claim 2, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase in a revascularization of a critically constricted coronary or peripheral artery.
- 20. The method of claim 2, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase in an acute myocardial infract, or due to medicinal or mechanical lysis thereof.
- 21. The method of claim 2, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase due to a tumor or metastasis of a tumor.
- 22. The method of claim 2, wherein the pharmaceutical composition is adapted for the treatment of a pathologically increased activity of poly(ATP-ribose)polymerase due to an immunological disease.
Priority Claims (1)
Number |
Date |
Country |
Kind |
198 52 816 |
Nov 1998 |
DE |
|
Parent Case Info
This application is a 371 of PCT/EP 99/08466 filed Nov. 5, 1999.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/EP99/08466 |
|
WO |
00 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO00/29384 |
5/25/2000 |
WO |
A |
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5395840 |
Miiller et al. |
Mar 1995 |
A |
Foreign Referenced Citations (2)
Number |
Date |
Country |
9704771 |
Feb 1997 |
WO |
9806703 |
Feb 1998 |
WO |