RU2001134010A - Optically Active Pyrrolopyridazine Derivatives - Google Patents

Claims (21)

Optically active pyrrolopyridazine derivative of formula (I) or a pharmaceutically acceptable salt thereof

in which R ¹ represents C ₁ -C ₆ alkyl; R ² and R ³ each independently represents C ₁ -C ₆ alkyl; R ⁴ represents C ₆ -C ₁₀ aryl, which is optionally substituted with one or more substituents selected from the group consisting of C ₁ -C ₆ alkyl, halogen C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, halogen C ₁ - C ₆ alkoxy and halogen; A represents an imino group, an oxygen atom or a sulfur atom. 2. The optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein R ¹ is C ₁ -C ₄ alkyl. 3. The optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein R ¹ is methyl. 4. The optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to one of claims 1 to 3, in which R ² and R ³ each independently represents C ₁ -C ₄ alkyl. 5. The optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, wherein R ² and R ³ are each methyl. 6. The optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, wherein R ⁴ is phenyl which is substituted by 1-3 substituents selected from the group consisting of C ₁ -C ₄ alkyl, halogen C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, halogen C ₁ -C ₄ alkoxy, fluoro, chloro and bromo. 7. The optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to one of claims 1 to 5, wherein R ⁴ is phenyl which is substituted by 1-3 substituents selected from the group consisting of methyl, trifluoromethyl, methoxy, trifluoromethoxy, difluoromethoxy, fluorine, chlorine and bromine. 8. The optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, wherein R ⁴ is phenyl which is substituted with 1 or 2 substituents selected from the group consisting of fluoro and chloro in position (s) selected from the group consisting of 2-, 4- and 6th positions of phenyl. 9. The optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, wherein R ⁴ is phenyl which is substituted with 1 or 2 substituents selected from the group consisting of fluorine and chlorine at the 4-position or in 2- and 4-position phenyl. 10. An optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, wherein A represents an oxygen atom or a sulfur atom. 11. An optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, wherein A represents an oxygen atom. 12. Optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof, selected from the group consisting of: 7- (4-fluorobenzyloxy) -2,3-dimethyl-1 - [(1S, 2S) -2-methylcyclopropylmethyl] pyrrolo [2, 3-d] pyridazine; 7- (2,4-difluorobenzyloxy) -2,3-dimethyl-1 - [(1S, 2S) -2-methylcyclopropylmethyl] pyrrolo [2,3-d] pyridazine; and 7- (4-chlorobenzyloxy) -2,3-dimethyl-1 - [(1S, 2S) -2-methylcyclopropylmethyl] pyrrolo [2,3-d] pyridazine. 13. A pharmaceutical composition comprising, as an active ingredient, an optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to one of claims 1 to 12. 14. An optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to one of claims 1 to 12 for use as a medicine. 15. An optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to one of claims 1 to 12, suitable as an active ingredient in a medicament for the treatment or prevention of peptic ulcer. 16. An agent containing an optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to one of claims 1 to 12 for use in the treatment or prevention of peptic ulcer. 17. A method of treating or preventing a disease in a warm-blooded animal, which comprises administering to a warm-blooded animal in need of such treatment or prevention, an effective amount of an optically active pyrrolopyridazine derivative or a pharmaceutically acceptable salt thereof according to one of claims 1-12. 18. The method according to 17, in which the disease is peptic ulcer. 19. The method according to claims 17-18, wherein the warm-blooded animal is a human being. 20. A method of obtaining an optically active pyrrolopyridazine derivative of formula (I) or a pharmaceutically acceptable salt thereof

in which R ¹ , R ² , R ³ , R ⁴ and A have the meanings defined below, which comprises reacting an optically active halogen pyrrolopyridazine derivative of formula (VI)

in which R ¹ represents C ₁ -C ₆ alkyl; R ² and R ³ each independently represents C ₁ -C ₆ alkyl; Y represents a halogen atom) with a compound of formula (VII)

in which R ⁴ represents C ₆ -C ₁₀ aryl, which is optionally substituted with one or more substituents selected from the group consisting of C ₁ -C ₆ alkyl, halogen C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, halogen C ₁ -C ₆ alkoxy and halogen;  A represents an imino group, an oxygen atom or a sulfur atom. 21. A method of obtaining an optically active pyrrolopyridazine derivative of formula (I) or a pharmaceutically acceptable salt thereof

in which R ¹ , R ² , R ³ , R ⁴ and A have the meanings defined below, which includes the interaction of a racemic derivative of halogenpyrrolopyridazine of the formula (VIa)

in which R ¹ represents C ₁ -C ₆ alkyl; R ² and R ³ each independently represents C ₁ -C ₆ alkyl; Y represents a halogen atom, with a compound of formula (VII)

in which R ⁴ represents C ₆ -C ₁₀ aryl, which is optionally substituted with one or more substituents selected from the group consisting of C ₁ -C ₆ alkyl, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy, C ₁ - C ₆ haloalkoxy and halogen; A represents an imino group, an oxygen atom or a sulfur atom; followed by optical separation of the racemic product.