Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-01-23
1997-07-29
Morris, Patricia L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5142332, 544126, 546 86, A61K 31435, C07D47106
Patent
active
056522452
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention is directed toward tricyclic nitrogen containing compounds, heterocyclic amines, having anxiolytic and anti-depressant activity. These new compounds are suitable for treating central nervous system disorders including schizophrenia, Parkinson's disease, anxiety or as compounds for lowering blood pressure or treating migraines.
A series of dihydropbenalenes, 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 anxiolytic activity 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 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 285-88 (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.
PCT Int. Pub. No. WO 90/15058 discloses compounds with the characteristic tricyclic nitrogen containing structure of the subject invention with the exception of the ring nitrogen "X" substituents.
SUMMARY OF THE INVENTION
In one aspect, the present invention is directed toward tricyclic nitrogen containing compounds of Formula I: ##STR2## and pharmaceutically acceptable salts thereof. R.sub.1 and R.sub.2 are independently hydrogen, C.sub.1-6 alkyl or R.sub.1 and R.sub.2 are joined to form pyrrolidine, piperidine, morpholine or imidazole. X is OCH.sub.3, SO.sub.2 R.sub.3, SO.sub.2 CF.sub.3 or CN where R.sub.3 is C.sub.1-6 alkyl or an Aryl; and Y is hydrogen, Cl, Br, F, CN, CONR.sub.1 R.sub.2, CF.sub.3, OCH.sub.3, SO.sub.2 NR.sub.1 R.sub.2.
These new compounds have been found to exhibit anxiolytic activity in isolation induced aggression and plasma corticosterone models. They are also suitable for treating various central nervous system disorders effected by 5-HT.sub.1A receptors such as, schizophrenia, Parkinson's disease, anxiety, depression, or as compounds for lowering blood pressure and treating migraine headaches in patients in need of such treatments.
In yet another aspect, the present invention is a method for treating central nervous system (CNS) disorders influenced by 5-HT.sub.1A receptors 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 compound of Formula I including pharmaceutically acceptable salts. Other uses for these compounds include panic attacks, eating disorders, obsessive-compulsive disturbances seen in dementia disorders. In addition, central 5-HT receptor activation are believed to be involved in mediating sexual behavior and therefore these compounds would be useful to stimulate sexual activity and to alleviate impotence.
DETAILED DESCRIPTION OF THE INVENTION
The present invention describes compounds of Formula I, above, having central nervous system activity. The compounds are characterized by a tricyclic ring structure having a shared nitrogen atom between two rings, an amine substituent (NR.sub.1 R.sub.2) and a substituted ring nitrogen (X) as structurally depicte
REFERENCES:
patent: 5151143 (1992-09-01), Inaba et al.
Corneglio Donald L.
Morris Patricia L.
Pharmacia & Upjohn Company
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