Claims
- 1. A compound of the Formula I ##STR9## and pharmaceutically acceptable acid addition salts thereof: wherein R.sub.a and R.sub.b are independently methyl, or ethyl, or when taken together with the carbon atom to which they are attached form a C.sub.3 -C.sub.6 cycloalkyl ring;
- E is O;
- R.sub.1 and R.sub.1a are independently hydrogen, methyl, halo, C.sub.1 -C.sub.3 alkoxy, (C.sub.1 -C.sub.3 alkyl)-S(O).sub.t -, trifluoromethyl, amino, hydroxy, (CH.sub.3).sub.2 NSO.sub.2 -, or (C.sub.1 -C.sub.4 alkyl)CONH;
- m is 1;
- t is 0,1, or 2;
- Z is O or NH; and
- R.sub.2 is quinuclidine, quinuclidine N-oxide, 1-azabicyclo[3.3.1]non-4-yl, ##STR10## wherein R.sub.3 is C.sub.1 -C.sub.3 alkyl, p and q are independently 0-2, Q is O or S; n is 0 or 1; one of R.sub.4 and R.sub.5 when n is 0 is C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkoxycarbonyl, hydroxy, C.sub.1 -C.sub.4 alkyl optionally substituted by hydroxy, C.sub.1 -C.sub.4 alkoxy, or C.sub.1 -C.sub.4 acyloxy and the other of R.sub.4 and R.sub.5 is hydrogen or C.sub.1 -C.sub.4 alkyl; one of R.sub.4, R.sub.5, and R.sub.6 when n is 1 is C.sub.1 -C.sub.4 alkyl and the other two of R.sub.4, R.sub.5, and R.sub.6 is independently hydrogen or C.sub.1 -C.sub.4 alkyl.
- 2. A compound of claim 1 which is of the formula ##STR11## wherein R.sub.1' is hydrogen, methyl, fluoro, bromo, or chloro, and R.sub.2' is endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl, 1-azabicyclo[2.2.2]oct-3-yl, or endo-9-methyl-9-azabicyclo[3.3.1]non-3-yl.
- 3. The compound which is endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 4. The compound of claim 2 which is 2,3-dihydro-5-chloro-2,2-dimethyl-N-(1-azabicyclo[2.2.2]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 5. The compound of claim 2 which is endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 6. The compound of claim 2 which is endo-2,3-dihydro-2,2-dimethyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 7. The compound of claim 2 which is 2,3-dihydro-2,2-dimethyl-N-(1-azabicyclo[2.2.2]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 8. A method of treating migraine, emesis, gastrointestinal disorders, schizophrenia, or anxiety in a mammal which comprises administering to said mammal an effective amount of a compound of claim 1.
- 9. A method of treating migraine, emesis, gastrointestinal disorders, schizophrenia, or anxiety in a mammal which comprises administering to said mammal an effective amount of a compound of claim 2.
- 10. A method of claim 9 employing endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 11. A method of claim 9 employing 2,3-dihydro-5-chloro-2,2-dimethyl-N-(1-azabicyclo[2.2.2]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 12. A method of claim 9 employing endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 13. A method of claim 9 employing endo-2,3-dihydro-2,2-dimethyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 14. A method of claim 9 employing 2,3-dihydro-2,2-dimethyl-N-(1-azabicyclo[2.2.2]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 15. A method of antagonizing 5-HT.sub.3 receptors in a mammal which comprises administering to said mammal an effective 5-HT.sub.3 -antagonizing amount of a compound of claim 1.
- 16. A method of antagonizing 5-HT.sub.3 receptors in a mammal which comprises administering to said mammal an effective 5-HT.sub.3 -antagonizing amount of a compound of claim 2.
- 17. The method of claim 16 employing endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 18. The method of claim 16 employing 2,3-dihydro-5-chloro-2,2-dimethyl-N-(1-azabicyclo[2.2.2]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 19. The method of claim 16 employing endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 20. The method of claim 16 employing endo-2,3-dihydro-2,2-dimethyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 21. The method of claim 16 employing 2,3-dihydro-2,2-dimethyl-N-(1-azabicyclo[2.2.2]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 22. A pharmaceutical formulation comprising a compound of claim 1 in association with a pharmaceutically acceptable carrier, diluent, or excipient.
- 23. A pharmaceutical formulation comprising a compound of claim 2 in association with a pharmaceutically acceptable carrier, diluent, or excipient.
- 24. A pharmaceutical formulation according to claim 23 wherein the compound is endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 25. A pharmaceutical formulation according to claim 23 wherein the compound is 2,3-dihydro-5-chloro-2,2-dimethyl-N-(1-azabicyclo[2.2.2]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 26. A pharmaceutical formulation according to claim 23 wherein the compound is endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 27. A pharmaceutical formulation according to claim 23 wherein the compound is endo-2,3-dihydro-2,2-dimethyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
- 28. A pharmaceutical formulation according to claim 23 wherein the compound is 2,3-dihydro-2,2-dimethyl-N-(1-azabicyclo[2.2.2]oct-3-yl)-7-benzofurancarboxamide or a pharmaceutically acceptable acid addition salt thereof.
CROSS-REFERENCE
This application is a division of Ser. No. 08/263,858 filed Jun. 22, 1994 now U.S. Pat. No. 5,442,078, which is a division of Ser. No. 08/053,061, filed Apr. 26, 1993, now U.S. Pat. No. 5,364,863, which is a division of Ser. No. 07/730,718, filed Jul. 16, 1991, now abandoned, which is a division of Ser. No. 07/598,297, filed Oct. 16, 1990, now abandoned, which is a division of Ser. No. 07/471,754, filed Jan. 24, 1990, now U.S. Pat. No. 4,997,956, which is a division of Ser. No. 07/366,343, filed Jun. 14, 1989, now U.S. Pat. No. 4,921,982, which is a continuation of Ser. No. 07/222,466, filed Jul. 21, 1988, now abandoned, which is a continuation-in-part of Ser. No. 07/094,360, filed Sep. 8, 1987, now abandoned.
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Divisions (6)
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Number |
Date |
Country |
Parent |
263858 |
Jun 1994 |
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Parent |
53061 |
Apr 1993 |
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Parent |
730718 |
Jul 1991 |
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Parent |
598297 |
Oct 1990 |
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Parent |
471754 |
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Parent |
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Continuations (1)
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Number |
Date |
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Parent |
222466 |
Jul 1988 |
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Continuation in Parts (1)
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Number |
Date |
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Parent |
94360 |
Sep 1987 |
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