Claims
- 1. A compound of the formula ##STR39## wherein D is ##STR40## wherein B is NH or O; wherein A is NH or a bond;
- wherein p is 1 or 0; and
- when p is 1, Ar is ##STR41## and when p is 0, Ar is ##STR42## wherein X is O,S,N(R.sup.4) or CH.sub.2 ; wherein Y is N or CH;
- wherein n is 1 or 2;
- wherein Z is ##STR43## wherein R.sup.1 is alkoxy of 1 to 6 carbon atoms; wherein R.sup.2 and R.sup.3 are the same or different and is hydrogen, halogen, CF.sub.3, hydroxyl, C.sub.1-2 alkoxy, C.sub.2-7 acyl, amino, amino substituted by one or two C.sub.1-6 alkyl groups, C.sub.2-7 acyl amino, amino carbonyl, or amino sulfone optionally substituted by one or two C.sub.1-6 alkyl groups, C.sub.1-6 alkyl sulfone or nitro groups;
- wherein R.sup.4 and R.sup.4 ' can be the same or different and is hydrogen, alkyl or arylalkyl; wherein R.sup.5 and R.sup.6 is the same or different and is hydrogen, halogen, CF.sub.3, C.sub.1-6 alkyl, C.sub.1-7 acyl, C.sub.1-7 acylamino, or amino, amino carbonyl or amino sulfonyl, optionally substituted by one or two C.sub.1-6 alkyl or C.sub.3-8 cycloalkyl groups, or by C.sub.4-5 polymethylene or biphenyl, C.sub.1-6 alkylsulfonyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, hydroxy or nitro or when R.sup.5 and R.sup.6 are taken together are methylenedioxy or ethylenedioxy;
- wherein R.sup.9 and R.sup.10 can be the same or different and is hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.1-4 alkynyl or together are C.sub.2-4 polymethylene;
- wherein R.sup.7 and R.sup.8 are the same or different and is hydrogen, halogen, CF.sub.3, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.1-7 acyl, C.sub.1-7 acylamino, C.sub.1-6 alkylsulfonylamino, N-(C.sub.1-6 alkylsulfonyl)-N-C.sub.1-4 alkylamino, C.sub.1-6 alkylsulfinyl, hydroxy, nitro or amino, aminocarbonyl, aminosulfonyl, aminosulfonylamino or N-(aminosulfonyl)-C.sub.1-4 alkylamino optionally N'-substituted by one or two groups selected from C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, phenyl, or phenyl C.sub.1-4 alkyl groups or optionally N'-disubstituted by C.sub.4-5 polymethylene; and wherein R.sup.11 and R.sup.12 can be the same or different and is hydrogen or C.sub.1-4 alkyl or taken together are a covalent bond; and
- wherein R.sup.13 is H, halogen or OR.sup.4.
- 2. A compound as recited in claim 1 wherein D is ##STR44##
- 3. A compound as recited in claim 2 wherein p is 1.
- 4. A compound as recited in claim 3 wherein B is NH.
- 5. A compound as recited in claim 4 wherein A is a covalent bond.
- 6. A compound as recited in claim 5 wherein Ar is ##STR45##
- 7. A compound as recited in claim 6 wherein
- R.sub.1 is methoxy;
- R.sub.2 is amino; and
- R.sub.3 is chloro.
- 8. A compound as recited in claim 7 having the structure ##STR46##
- 9. A compound as recited in claim 5 wherein Ar is ##STR47##
- 10. A compound as recited in claim 9 wherein X is NH.
- 11. A compound as recited in claim 5 wherein Ar is ##STR48##
- 12. A compound as recited in claim 5 wherein Ar is ##STR49##
- 13. A compound as recited in claim 12 wherein R.sup.4 is a methyl group.
- 14. A compound as recited in claim 5 wherein Ar is ##STR50##
- 15. A compound as recited in claim 4 wherein A is NH.
- 16. A compound as recited in claim 15 wherein Ar is ##STR51##
- 17. A compound as recited in claim 15 wherein Ar is ##STR52##
- 18. A compound as recited in claim 15 wherein Ar is ##STR53##
- 19. A compound as recited in claim 15 wherein Ar is ##STR54##
- 20. A compound as recited in claim 15 wherein Ar is ##STR55##
- 21. A compound as recited in claim 3 wherein B is 0.
- 22. A compound as recited in claim 2 wherein p is 0.
- 23. A compound as recited in claim 22 wherein Ar is ##STR56##
- 24. A compound as recited in claim 22 wherein Ar is ##STR57##
- 25. A compound as recited in claim 1 wherein D is ##STR58##
- 26. A compound as recited in claim 25 wherein p is 1.
- 27. A compound as recited in claim 26 wherein B is NH.
- 28. A compound as recited in claim 27 wherein A is a covalent bond.
- 29. A compound as recited in claim 28 wherein Ar is ##STR59##
- 30. A compound as recited in claim 29 wherein
- R.sub.1 is methoxy;
- R.sub.2 is amino; and
- R.sub.3 is chloro.
- 31. A compound as recited in claim 28 wherein Ar is ##STR60##
- 32. A compound as recited in claim 28 wherein Ar is ##STR61##
- 33. A compound as recited in claim 28 wherein Ar is ##STR62##
- 34. A compound as recited in claim 28 wherein Ar is ##STR63##
- 35. A compound as recited in claim 27 wherein A is NH.
- 36. ##STR64##
- 37. A compound as recited in claim 35 wherein Ar is ##STR65##
- 38. A compound as recited in claim 35 wherein Ar is ##STR66##
- 39. A compound as recited in claim 35 wherein Ar is ##STR67##
- 40. A compound as recited in claim 35 wherein Ar is ##STR68##
- 41. A compound as recited in claim 26 wherein B is 0.
- 42. A compound as recited in claim 25 wherein p is 0.
- 43. A compound as recited in claim 42 wherein Ar is ##STR69##
- 44. A compound as recited in claim 42 wherein Ar is ##STR70##
- 45. A pharmaceutical composition comprising therapeutically or prophylactically effective amount of a compound of claim 1 of the formula ##STR71## and a pharmaceutical carrier.
- 46. A pharmaceutical composition as recited in claim 45 wherein D is ##STR72##
- 47. A pharmaceutical composition as recited in claim 45 wherein D is ##STR73##
- 48. A method of treating gastrointestinal motility disorders comprising administering to a patient in need of such treatment, a therapeutically effective amount of a compound according to claim 2 and a pharmaceutically acceptable carrier.
- 49. A method of treating gastrointestinal motility disorders comprising administering to a patient in need of such treatment, a therapeutically effective amount of a compound according to claim 25 and a pharmaceutically acceptable carrier.
- 50. A method of preventing emesis or ileus comprising administering to a patient in need of such treatment, a therapeutically effective amount of a compound according to claim 2 in a pharmaceutically acceptable carrier.
- 51. A method for preventing emesis or ileus comprising administering to a patient in need of such treatment, a therapeutically effective amount of a compound according to claim 25 in a pharmaceutically acceptable carrier.
- 52. A method of treating emesis, anxiety, pain, schizophrenia, depression, substance abuse, memory impairment, or related diseases having a serotonergic etiology benefiting from use of a serotonergic 5-HT.sub.3 antagonist comprising administering to a patient in need of such treatment, a therapeutically effective amount of a compound according to claim 2 and a pharmaceutically acceptable carrier.
Parent Case Info
This application is a .Iadd.reissue of Ser. No. 07/682,993 filed Apr. 12, 1991, now U.S. Pat. No. 5,140,023 which is a .Iaddend.continuation-in-part of U.S. patent application Ser. No. 07/515,391 filed Apr. 27, 1990, now abandoned.
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Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
515391 |
Apr 1990 |
|
Reissues (1)
|
Number |
Date |
Country |
Parent |
682993 |
Apr 1991 |
|