Claims
- 1. A pyrrolopyridazine compound having the following formula or a pharmaceutically acceptable salt thereof: wherein: R1 is selected from the group consisting of C2-C6 alkenyl groups, halogeno C2-C6 alkenyl groups, C3-C7 cycloalkyl groups which may be optionally substituted with a C1-C6 alkyl group and C3-C7 cycloalkyl-C1-C6 alkyl groups which may be optionally substituted with a C1-C6 alkyl group; R2 represents a C1-C6 alkyl group; R3 is selected from the group consisting of hydroxymethyl groups, C2-C6 aliphatic acyloxymethyl groups, C6-C10 arylcarbonyloxymethyl groups which may be optionally substituted with substituents selected from the group consisting of C1-C6 alkyl groups, C1-C6 alkoxy groups and halogen atoms, C1-C6 alkoxycarbonyloxymethyl groups, formyl groups, carboxyl groups, C1-C6 alkoxycarbonyl groups and C6-C10 aryloxycarbonyl groups which may be optionally substituted with substituents selected from the group consisting of C1-C6 alkyl groups, C1-C6 alkoxy groups and halogen atoms; R4 represents a C6-C10 aryl group which may be optionally substituted with substituents selected from the group consisting of C1-C6 alkyl groups, halogeno C1-C6 alkyl groups, C1-C6 alkoxy groups, halogeno C1-C6 alkoxy groups and halogen atoms; and A is selected from the group consisting of imino groups, oxygen atoms and sulfur atoms.
- 2. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R1 is selected from the group consisting of C2-C4 alkenyl groups, C3-C4 alkenyl groups substituted with fluoro or chloro, C3-C6 cycloalkyl groups which may be optionally substituted with a C1-C2 alkyl group and C3-C6 cycloalkyl-C1-C2 alkyl groups which may be optionally substituted with a C1-C2 alkyl group.
- 3. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R1 is selected from the group consisting of C3-C4 alkenyl groups, 3-chloro-2-propenyl groups, 3,3-difluoro-2-propenyl groups, 3,3-dichloro-2-propenyl groups, cyclopropyl groups, 2-methylcyclopropyl groups, 2-ethylcyclopropyl groups, cyclobutyl groups, cyclopentyl groups, 2-methylcyclopentyl groups, cyclohexyl groups, 2-methylcyclohexyl groups, cyclopropylmethyl groups, 2-methylcyclopropylmethyl groups, 2-ethylcyclopropylmethyl groups, cyclobutylmethyl groups, 2-methylcyclobutylmethyl groups, cyclopentylmethyl groups and 2-methylcyclohexylmethyl groups.
- 4. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R1 is selected from the group consisting of 2-propenyl groups, 2-butenyl groups, cyclopropyl groups, 2-methylcyclopropyl groups, cyclopentyl groups, 2-methylcyclopentyl groups, cyclohexyl groups, 2-methylcyclohexyl groups, cyclopropylmethyl groups, 2-methylcyclopropylmethyl groups, cyclopentylmethyl groups and 2-methylcyclohexylmethyl groups.
- 5. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R1 is selected from the group consisting of 2-propenyl groups, 2-butenyl groups, cyclopropyl groups, 2-methylcyclopropyl groups, cyclopropylmethyl groups and 2-methylcyclopropylmethyl groups.
- 6. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R1 is selected from the group consisting of 2-butenyl groups, cyclopropylmethyl groups and 2-methylcyclopropylmethyl groups.
- 7. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R2 is a C1-C4 alkyl group.
- 8. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R2 is a C1-C2 alkyl group.
- 9. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R2 is a methyl group.
- 10. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R3 is selected from the group consisting of hydroxymethyl groups, C2-C6 aliphatic acyloxymethyl groups, benzoyloxymethyl groups which may be optionally substituted with a substituent selected from the group consisting of methyl groups, methoxy groups, fluoro and chloro, C1-C4 alkoxycarbonyloxymethyl groups, formyl groups, carboxyl groups, C1-C4 alkoxycarbonyl groups and phenyloxycarbonyl groups which may be optionally substituted with a substituent selected from the group consisting of methyl groups, methoxy groups, fluoro and chloro.
- 11. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R3 is selected from the group consisting of hydroxymethyl groups, C2-C6 aliphatic acyloxymethyl groups, benzoyloxymethyl groups, C1-C2 alkoxycarbonyloxymethyl groups, formyl groups, carboxyl groups, C1-C2 alkoxycarbonyl groups and phenyloxycarbonyl groups.
- 12. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R3 is selected from the group consisting of hydroxymethyl groups, C2-C4 aliphatic acyloxymethyl groups, C1-C2 alkoxycarbonyloxymethyl groups, formyl groups, carboxyl groups and C1-C2 alkoxycarbonyl groups.
- 13. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R3 is selected from the group consisting of hydroxymethyl groups, C2-C3 aliphatic acyloxymethyl groups, formyl groups and carboxyl groups.
- 14. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R3 is a hydroxymethyl group or an acetoxymethyl group.
- 15. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R4 is a phenyl group which is substituted with 1 to 3 substituents selected from the group consisting of C1-C4 alkyl groups, halogeno C1-C4 alkyl groups, C1-C4 alkoxy groups, halogeno C1-C4 alkoxy groups, fluoro, chloro and bromo.
- 16. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R4 is a phenyl group which is substituted with 1 to 3 substituents selected from the group consisting of a methyl group, a trifluoromethyl group, a methoxy group, a trifluoromethoxy groups, a difluoromethoxy group, fluoro, chloro and bromo.
- 17. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R4 is a phenyl group which is substituted at the position(s) selected from the group consisting of 2-, 4- and 6-position of the phenyl group with 1 or 2 substituents selected from the group consisting of fluoro and chloro.
- 18. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R4 is a phenyl group which is substituted at the 4-position, 2,4-positions or 2,6-positions of the phenyl group with 1 or 2 substituents selected from the group consisting of fluoro and chloro.
- 19. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein A is an oxygen atom or a sulfur atom.
- 20. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein A is an oxygen atom.
- 21. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein:R1 is selected from the group consisting of C2-C4 alkenyl groups, C3-C4 alkenyl groups substituted with fluoro or chloro, C3-C6 cycloalkyl groups which may be optionally substituted with a C1-C2 alkyl group and C3-C6 cycloalkyl-C1-C2 alkyl groups which may be optionally substituted with a C1-C2 alkyl group; R2 is a C1-C4 alkyl group; R3 is selected from the group consisting of hydroxymethyl groups, C2-C6 aliphatic acyloxymethyl groups, benzoyloxymethyl groups which may be optionally substituted with a substituent selected from the group consisting of methyl groups, methoxy groups, fluoro and chloro, C1-C4 alkoxycarbonyloxymethyl groups, formyl groups, carboxyl groups, C1-C4 alkoxycarbonyl groups and phenyloxycarbonyl groups which may be optionally substituted with a substituent selected from the group consisting of methyl groups, methoxy groups, fluoro and chloro; R4 is a phenyl group which is substituted with 1 to 3 substituents selected from the group consisting of C1-C4 alkyl, halogeno C1-C4 alkyl, C1-C4 alkoxy, halogeno-C1-C4 alkoxy, fluoro, chloro and bromo; and A is an oxygen atom or a sufur atom.
- 22. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein:R1 is selected from the group consisting of C3-C4 alkenyl groups, 3-chloro-2-propenyl groups, 3,3-difluoro-2-propenyl groups, 3,3-dichloro-2-propenyl groups, cyclopropyl groups, 2-methylcyclpropyl groups, 2-ethylcyclopropyl groups, cyclobutyl groups, cyclopentyl groups, 2-methylcyclopentyl groups, cyclohexyl groups, 2-methylcyclohexyl groups, cyclopropylmethyl groups, 2-methylcyclopropylmethyl groups, 2-ethylcyclopropylmethyl groups, cyclobutylmethyl groups, 2-methylcyclobutylmethyl groups, cyclopentylmethyl groups and 2-methylcyclohexylmethyl groups; R2 is a C1-C4 alkyl group; R3 is selected from the group consisting of hydroxymethyl groups, C2-C6 aliphatic acyloxymethyl groups, benzoyloxymethyl groups, C1-C2 alkoxycarbonyloxymethyl groups, formyl groups, carboxyl groups, C1-C2 alkoxycarbonyl groups and phenyloxycarbonyl groups; R4 is a phenyl group which is substituted with 1 to 3 substituents selected from the group consisting of methyl groups, trifluoromethyl groups, methoxy groups, trifluoromethoxy groups, difluoromethoxy groups, fluoro, chloro and bromo; and A is an oxygen atom or a sulfur atom.
- 23. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein:R1 is selected from the group consisting of 2-propenyl groups, 2-butenyl groups, cyclopropyl groups, 2-methylcyclopropyl groups, cyclopentyl groups, 2-methylcyclopentyl groups, cyclohexyl groups, 2-methylcyclohexyl groups, cyclopropylmethyl groups, 2-methylcyclopropylmethyl groups, cyclopentylmethyl groups and 2-methylcyclohexylmethyl groups; R2 is a C1-C2 alkyl group; R3 is selected from the group consisting of hydroxymethyl groups, C2-C4 aliphatic acyloxymethyl groups, C1-C2 alkoxycarbonyloxymethyl groups, formyl groups, carboxyl groups and C1-C2 alkoxycarbonyl groups; R4 is a phenyl group which is substituted at the position(s) selected from the group consisting of 2-, 4- and 6-position of the phenyl group with 1 or 2 substituents selected from the group consisting of fluoro and chloro; and A is an oxygen atom.
- 24. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein:R1 is selected from the group consisting of 2-propenyl groups, 2-butenyl groups, cyclopropyl groups, 2-methylcyclopropyl groups, cyclopropylmethyl groups and 2-methylcyclopropylmethyl groups, R2 is a C1-C2 alkyl group; R3 is selected from the group consisting of hydroxymethyl groups, C2-C3 aliphatic acyloxymethyl groups, formyl groups and carboxyl groups; R4 is a phenyl group which is substituted at the position(s) selected from the group consisting of 2-, 4- and 6-position of the phenyl group with 1 or 2 substituents selected from the group consisting of fluoro and chloro; and A is an oxygen atom.
- 25. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein:R1 is selected from the group consisting of 2-butenyl groups, cyclopropylmethyl groups and 2-methylcyclopropylmethyl groups; R2 is a methyl group; R3 is a hydroxymethyl group or an acetoxymethyl group; R4 is a phenyl group which is substituted at the 4-position, 2,4-positions or, 2,6-positions of the phenyl group with 1 or 2 substituents selected from the group consisting of fluoro and chloro; and A is an oxygen atom.
- 26. A pyrrolopyridazine compound selected from the following group or a pharmaceutically acceptable salt thereof:1-(2-butenyl)-7-(4-fluorobenzyloxy)-3-hydroxymethyl-2-methylpyrrolo[2,3-d]pyridazine, 7-(4-fluorobenzyloxy)-3-hydroxymethyl-2-methyl-1-(2-methylcyclopropylmethyl)pyrrolo[2,3-d]pyridazine, 1-(2-butenyl)-7-(2,4-difluorobenzyloxy)-3-hydroxymethyl-2-methylpyrrolo[2,3-d]pyridazine, 7-(2,4-difluorobenzyloxy)-3-hydroxymethyl-2-methyl-1-(2-methylcyclopropylmethyl)pyrrolo[2,3-d]pyridazine, 3-acetoxymethyl-7-(4-fluorobenzyloxy)-2-methyl-1-(2-methylcyclopropylmethyl)pyrrolo[2,3-d]pyridazine, and 3-acetoxymethyl-7-(2,4-difluorobenzyloxy)-2-methyl-1-(2-methylcyclopropylmethyl)pyrrolo[2,3-d]pyridazine.
- 27. A pyrrolopyridazine compound according to claim 26.
- 28. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, which is 3-acetoxymethyl-7-(4-fluorobenzyloxy)-2-methyl-1-[(1S,2S)-2-methylcyclopropylmethyl]pyrrolo[2,3-d]pyridazine or a pharmaceutically acceptable salt thereof.
- 29. A pyrrolopyridazine compound according to claim 28.
- 30. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, which is 7-(4-fluorobenzyloxy)-3-hydroxymethyl-2-methyl-1-[(1S,2S) -2-methylcyclopropylmethyl]pyrrolo[2,3-d]pyridazine or a pharmaceutically acceptable salt thereof.
- 31. A pyrrolopyridazine compound according to claim 30.
- 32. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, which is 7-(4-fluorobenzyloxy)-3-formyl-2-methyl-1-[(1S,2S)-2-methylcyclopropylmethyl]pyrrolo[2,3-d]pyridazine or a pharmaceutically acceptable salt thereof.
- 33. A pyrrolopyridazine compound according to claim 32.
- 34. A pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to claim 1, which is 3-carboxy-7-(4-fluorobenzyloxy)-2-methyl-1-[(1S,2S)-2-methylcyclopropylmethyl]pyrrolo[2,3-d]pyridazine or a pharmaceutically acceptable salt thereof.
- 35. A pyrrolopyridazine compound according to claim 34.
- 36. A pharmaceutical composition comprising (i) a pharmacologically acceptable carrier and (ii) a pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 35.
- 37. A method for the prophylaxis or treatment of an ulcerative disease which comprises administering to a warm-blooded animal in need thereof a pharmaceutically effective amount of a pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to anyone of claims 1 to 35.
- 38. A method for the prophylaxis or treatment of an ulcerative disease which comprises administering to a human in need thereof a pharmaceutically effective amount of a pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to anyone of claims 1 to 35.
- 39. A method for the treatment of a Helicobacter pylori infection in a warm-blooded animal which comprises administering to said warm-blooded animal a pharmaceutically effective amount of a pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to anyone of claims 1 to 20.
- 40. A method for the treatment of a Helicobacter pylori infection in a human which comprises administering to said human a pharmaceutically effective amount of a pyrrolopyridazine compound or a pharmaceutically acceptable salt thereof according to anyone of claims 21 to 35.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 2000-033627 |
Feb 2000 |
JP |
|
Parent Case Info
This is a continuation application of international application PCT/JP01/00820 filed Feb. 6, 2001.
US Referenced Citations (4)
Foreign Referenced Citations (4)
| Number |
Date |
Country |
| 1 186 607 |
Mar 2002 |
EP |
| WO 9117164 |
Nov 1991 |
WO |
| WO 9206979 |
Apr 1992 |
WO |
| WO 0077003 |
Dec 2000 |
WO |
Non-Patent Literature Citations (2)
| Entry |
| U.S. patent application Ser. No. 10/021,214, Hagihara et al., not yet published. |
| English language translation of the International Preliminary Examination Report PCT/IPEA/409 in the parent International Application PCT/JP01/00820 (date of completion of Report: Jan. 17, 2002). |
Continuations (1)
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Number |
Date |
Country |
| Parent |
PCT/JP01/00820 |
Feb 2001 |
US |
| Child |
10/215246 |
|
US |
Patent Grant
6734181
