Claims
- 1. A tetrahydrobenzimidazole derivative represented by formula (I): ##STR60## wherein Het represents a member selected from the group consisting of pyrollidine, piperidine, piperazine, morpholine, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, isoxazole, isothiazole, triazole, thiadiazole, oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, 4H-cyclopentathiazole, indole, isoindole, 2,3-dihydroindole (indoline), isoindoline, hydroxyindole, indazole, indolizine, benzothiophene, benzofuran, benzothiazole, benzimidazole, benzoxazole, 4,5,6,7-tetrahydrobenzothiophene, 2,3-dihydrobenzimidazol-2-one, quinoline, isoquinoline, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, 1,4-benzoxazine, phenothiazine, carbazole and .beta.-carboline, and wherein Het may be substituted with 1 to 3 substituents selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl-lower alkyl, aralkyl, lower alkoxy, nitro, hydroxyl, lower alkoxycarbonyl, and halo; and X represents a single bond or --NH-- which is bonded to the carbon atom or nitrogen atom of the heterocyclic ring of said Het, or a pharmaceutically acceptable salt thereof.
- 2. The derivative as claimed in claim 1 wherein X represents a single bond.
- 3. The derivative as claimed in claim 1 wherein X represents a single bond connected to a nitrogen atom of the Het group.
- 4. The derivative as claimed in claim 1 wherein X represents --NH--.
- 5. The derivative as claimed in claim 1 wherein Het is pyrrolidinyl.
- 6. The derivative as claimed in claim 1 wherein Het is 1,2,3,4-tetrahydroisoquinolinyl.
- 7. The derivative as claimed in claim 1 wherein Het is 2,3-dihydrobenzimidazol-2-one-yl.
- 8. The derivative as claimed in claim 1 wherein Het is N-(2-benzothiazolyl).
- 9. The derivative as claimed in claim 1 wherein Het represents a member selected from the group consisting of pyrrolidine, pyrrole, furan, thiophene, imidazole, pyrazole, isoindole, 2,3-dihydrobenzimidazole-2-one, isoindoline, hydroxyindole, indazole, benzothiophene, benzofuran, benzimidazole, 4,5,6,7-tetrahydrobenzothiophene, carbazole and beta-carboline.
- 10. The derivative as claimed in claim 1 wherein Het is indole.
- 11. The derivative as claimed in claim 1 wherein Het is 2,3-dihydroindol.
- 12. A compound as claimed in claim 1, wherein Het is represented by the formula: ##STR61## wherein R.sup.1 represents hydrogen, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl-lower alkyl, or an aralkyl; R.sup.2 represents hydrogen, lower alkyl, or aralkyl; and R.sup.3 represents hydrogen, lower alkoxy, nitro, hydroxyl, lower alkoxycarbonyl, or halo; and X represents a single bond.
- 13. A compound as claimed in claim 1, wherein Het represents a nitrogen-containing heterocyclic group; and X is a single bond connected to the nitrogen atom of the nitrogen-containing heterocyclic ring.
- 14. A compound as claimed in claim 12, wherein said compound is 5-[(1-methylindol-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole.
- 15. A compound as claimed in claim 1, wherein said compound is an (R)-compound.
- 16. A compound as claimed in claim 1, wherein said compound is an (S)-compound.
- 17. A compound as claimed in claim 1, wherein said compound is 5-[[1-(2-propynyl)indol-3-yl]carbonyl]-4,5,6,7-tetrahydrobenzimidazole.
- 18. A compound as claimed in claim 1, wherein said compound is 5-[(2,3-dihydroindol-1-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole.
- 19. A compound as claimed in claim 1, wherein said compound is 1-[(4,5,6,7-tetrahydrobenzimidazole-5-Yl)carbonyl]-2,3-dihydrobenzimidazol-2-one.
- 20. A compound as claimed in claim 1, wherein said compound is 5-[(2-benzylindol-3-yl)-carbonyl]-4,5,6,7-tetrahydrobenzimidazole.
- 21. A compound as claimed in claim 1, wherein said compound is 5-[(1-n-butylindol-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole.
- 22. A compound as claimed in claim 1, wherein said compound is 5-[(1-cyclohexylmethylindol-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole
- 23. A compound as claimed in claim 1, wherein said compound is 5-[1-benzylindol-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole.
- 24. A compound as claimed in claim 1, wherein said compound is N-(pyridin-3-yl)-4,5,6,7-tetrahydrobenzimidazole-5-carboxamide.
- 25. A compound as claimed in claim 1, wherein said compound is N-(5,6-dihydro-4H-cyclopentathiazol-2-yl)-4,5,6,7-tetrahydrobenzimidazole-5-carboxamide.
- 26. A pharmaceutical composition containing a tetrahydrobenzimidazole derivative represented by the following formula (I) or a pharmaceutically acceptable salt thereof: ##STR62## wherein Het represents a member selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, pyrrole, furan thiophene, imidazole, oxazole, thiazole, pyrazole, isoxazole, isothiazole, triazole, thiadiazole, oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, 4H-cyclopentathiazole, indole, isoindole, 2,3-dihydroindole (indoline), isoindoline, hydroxyindole, indazole, indolizine, benzothiophene, benzofuran, benzothiazole, benzimidazole, benzoxazole, 4,5,6,7-tetrahydrobenzothiophene, 2,3,-dihydrobenzimidazol-2-one, quinoline, isoquinoline, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, 1,4-benzoxazine, phenothiazine, carbazole and .beta.-carboline, and wherein Het may be substituted with 1 to 3 substituents selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl lower alkyl aralkyl, lower alkoxy, nitro, hydroxyl, lower alkoxycarbonyl, and halo; and X represents a single bond or --NH-- which is bonded to the carbon atom or nitrogen atom of the heterocyclic ring, and a pharmaceutically acceptable carrier.
- 27. A pharmaceutical composition as claimed in claim 26, wherein said composition is a 5HT.sub.3 -antagonist.
- 28. A pharmaceutical composition as claimed in claim 26, wherein said composition is a treating agent for gastrointestinal disorders.
- 29. A pharmaceutical composition as claimed in claim 26, wherein said gastrointestinal disorders are anaphylactic intestinal syndrome.
- 30. A pharmaceutical composition as claimed in claim 26, wherein said composition is a treating agent for nausea and/or vomiting induced by chemotherapy or radiation.
- 31. A pharmaceutical composition as claimed in claim 26, wherein said composition is a treating agent for migraine, cluster headache and trigeminal neuralgia.
- 32. A pharmaceutical composition as claimed in claim 26, wherein said composition is a treating agent for anxiety and psychotic disorders.
Priority Claims (4)
Number |
Date |
Country |
Kind |
1-25397 |
Feb 1989 |
JPX |
|
1-48897 |
Feb 1989 |
JPX |
|
1-273444 |
Oct 1989 |
JPX |
|
1-342939 |
Dec 1989 |
JPX |
|
Parent Case Info
This application is a continuation of application Ser. No. 07/713,890, filed Jun. 12, 1991, now abandoned, which is a continuation of application Ser. No. 07/567,949, filed Aug. 15, 1990, now abandoned, which in turn is a continuation-in-part of application Ser. No. 07/470,950, filed Jan. 26, 1990, now abandoned.
US Referenced Citations (7)
Continuations (2)
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Number |
Date |
Country |
Parent |
713890 |
Jun 1991 |
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Parent |
567949 |
Aug 1990 |
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Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
470950 |
Jan 1990 |
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