Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1991-12-06
1993-12-28
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514253, 514291, 514292, 514293, 514294, 544126, 544361, 546 80, 546 82, 546 83, 546 84, 546 89, 546 94, A61K 31495, A61K 3150, C07D51302, C07D47106
Patent
active
052739759
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention is directed toward tricyclic nitrogen containing compounds, heterocyclic amines, having central nervous system activity. These new compounds are suitable for treating schizophrenia, Parkinson's disease, anxiety or as compounds for lowering blood pressure.
A series of dihydrophenalenes, tricyclic amine substituted compounds, and related compounds having central nervous system activity were described in PCT Int. Pub. No. WO87/04153 and in PCT Int. Pub. No. WO88/04292. A major difference between those compounds and the present invention is that the subject compounds have at least one nitrogen atom in the tricyclic ring structure which is shared by two of the ring structures. Generally, the subject compounds have exhibited antipsychotic acitivity and better oral bioavailability.
Information Disclosure Statement
PCT Int. Pub. No. WO87/04153 and PCT Int. Pub. No. WO88/04292 each describe tricyclic structures having central nervous system activity.
U.S. Pat. No. 4,110,339 discloses 4-(di-n-propyl)amino-1,3,4,5-tetrahydrobenz(cd)indole compounds useful as prolactin inhibitors and in the treatment of Parkinsonism. European Patent Application 153,083 and German Patent No. 3,346,573 disclose methoxy substituted 4 -(di-n-propyl)amino-1,3,4,5-tetrahydrobenz(cd)indole compounds. These publications disclose nitrogen containing tricyclic ring structures but the nitrogen is not shared by any of the rings.
Evans, D. D., Peters, D. J., J. Chem. Soc., Perkin Trans. 1, pp 285-288 (1974) discloses nitrogen containing tricyclic ring structures where the nitrogen is shared by two ring structures but additionally includes other substituents not common to the subject compounds.
SUMMARY OF THE INVENTION
In the aspect, the present invention is directed toward tricyclic nitrogen containing compounds of Formula I, having central nervous system activity and pharmaceutically acceptable salts. R.sub.1, R.sub.2, and R.sub.3 are independently hydrogen, C.sub.1-6 alkyl, C.sub.3-5 alkenyl, or C.sub.3-5 alkynyl, C.sub.3-7 cycloalkyl or C.sub.4-10 cycloalkyl- or phenyl-substituted alkyl, or R.sub.1 and R.sub.2 are joined to form a C.sub.3-7 cyclic amine which can contain additional heteroatoms and/or unsaturation. X is hydrogen, C.sub.1-6 alkyl, halogen, hydroxy, alkoxy, cyano, carboxamide, carboxyl, or carboalkoxyl. A is SO.sub.2, N, CH, CH.sub.2, CHCH.sub.3, C.dbd.O, C.dbd.S, C--SCH.sub.3, C.dbd.NH, C--NH.sub.2, C--NHCH.sub.3, C--NHCOOCH.sub.3, or C--NHCN. B is CH.sub.2, CH, C.dbd.O, N, NH or N--CH.sub.3 and n is 0 or 1. D is CH.sub.2, C.dbd.O, O, N, NH or N--CH.sub.3. These new compounds are suitable for treating schizophrenia, Parkinson's disease, anxiety, depression, or as compounds for lowering blood pressure.
In another aspect, the invention is a novel compound of the structural formula XXXV' where W is O or H.sub.2 and R.sub.1 'and R.sub.2 are independently hydrogen or a C.sub.1-4 alkyl group. This compound is useful as an intermediate in the preparation of compounds of Formula I. Preferred compounds are where W is H.sub.2 and R.sub.1 and R.sub.2 are the same such as CH.sub.3 or C.sub.3 H.sub.2 groups.
In yet another aspect, the present invention is a method for treating central nervous system (CNS) disorders such as anxiety, depression, hypertension and associated high blood pressure, Parkinson's disease and schizophrenia in animal or human hosts by administering a pharmaceutically effective amount of a commond of Formula I including pharmaceutically acceptable salts. Other uses for these compounds include panic attacks, eating disorders, obsessive-compulsive disturbances seen in demantia disorders. In addition, central 5-HT receptor activation are believed to be involved in mediating sexual behavior. These compounds would be useful to stimulate sexual activity and to alleviate impotence.
DETAILED DESCRIPTION OF THE INVENTION
The present invention describes compounds having central nervous system activity. The compounds are identified by a tricyclic ring structure having a nit
REFERENCES:
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Evans, D. D. et al., "1,3,4,5-Tetrahydrobenz[cd]indoles and Related Compounds. Part V. Some Reactions of 1,2,4,5-Tetrahydropyrrolo[3,2,1-ij]quinolin-6-one", J. S. C. Perkin I, 285-88 (1974).
K. Sempuku, "Tetracyclic Compounds", Chemical Abstract 95:62240y, 1981.
Heier Richard F.
Moon Malcolm W.
Morris Jeanette K.
Corneglio Donald L.
Grumbling Matthew V.
Shah Mukund J.
The Upjohn Company
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