Derivatives of quinuclidine n-oxide as muscarinic receptor ligan

Details Derivatives of quinuclidine n-oxide as muscarinic receptor ligan Derivatives of quinuclidine n-oxide as muscarinic receptor ligan

1996-11-12

1997-10-07

Ivy, C. Warren

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

514305, C07D21194, C07D22122, A61K 31435

Patent

active

056750072

DESCRIPTION:

BRIEF SUMMARY
This application is the U.S. National phase of PCT/EP95/01758 filed May 9, 1995; published as WO95/31457 on Nov. 23, 1995.
This invention relates to a compound having pharmaceutical activity, to a process for its preparation and its use as a pharmaceutical.
EP-A-0392803 (Beecham Group p.l.c.) discloses certain azabicyclic compounds which enhance acetylcholine function via an action at muscarinic receptors within the central nervous system, including rile and its enantiomers.
A novel compound has now been discovered which also enhances acetylcholine function via an action at muscarinic receptors within the central nervous system and is therefore of potential use in the treatment and/or prophylaxis of dementia in mammals.
According to the present invention, there is provided a compound of formula (I) or a pharmaceutically acceptable salt thereof. ##STR1## wherein R.sub.1 represents ##STR2##
R.sub.2 is a group OCH.sub.3, and
R.sub.3 is cyano.
The compound of formula (I) is capable of existing in a number of stereoisomeric forms including geometric isomers such as E and Z and enantiomers. The invention extends to each of these stereoisomeric forms, and to mixtures thereof (including racemates). The different stereoisomeric forms may be separated one from the other by the usual methods, or any given isomer may be obtained by stereospecific or asymmetric synthesis.
The compound of formula (I) is preferably in pharmaceutically acceptable form. By pharmaceutically acceptable form is meant, inter alia, of a pharmaceutically acceptable level of purity excluding normal pharmaceutical additives such as diluents and carriers, and including no material considered toxic at normal dosage levels. A pharmaceutically acceptable level of purity will generally be at least 50% excluding normal pharmaceutical additives, preferably 75%, more preferably 90% and still more preferably 95%. One preferred pharmaceutically acceptable form is the crystalline form, including such form in a pharmaceutical composition.
The compound of formula (I) can form acid addition salts with strong acids. The term pharmaceutically acceptable salt encompasses solvates and hydrates. Thus, where the compound of formula (I) or pharmaceutically acceptable salts thereof forms solvates or hydrates, these also form an aspect of the invention.
The invention also provides a process for the preparation of the compound of formula (I), or a pharmaceutically acceptable salt thereof, which process comprises: ##STR3## with a compound of formula (III):
wherein R.sub.2 ' represents R.sub.2 or hydroxy, and R.sub.1 ' and R.sub.3 ' represent R.sub.1 and R.sub.3 or groups convertible thereto, and thereafter converting R.sub.2 ' to R.sub.2 when hydroxy, and converting R.sub.1 ' and R.sub.3 ' when other than R.sub.1 and R.sub.3 to R.sub.1 and R.sub.3, wherein R.sub.1, R.sub.2 and R.sub.3 are as defined in formula (I); ##STR4## wherein R'.sub.1 is R.sub.1 or a group convertible thereto, with a compound of formula (V): R.sub.1 ' when other than R.sub.1 to R.sub.1, wherein R.sub.1, R.sub.2 and R.sub.3 are as defined in formula (I); ##STR5##
wherein R.sub.1 ' is R.sub.1 or a group convertible thereto, and R.sub.3 " is an electron withdrawing group, and thereafter converting the resulting .dbd.NOH group to .dbd.NR.sub.2 and converting R.sub.1 ' and R.sub.3 " when other than R.sub.1 and R.sub.3 to R.sub.1 and R.sub.3, wherein R.sub.1, R.sub.2 and R.sub.3 are as defined in formula (I); ##STR6## wherein R.sub.1 ' is R.sub.1 or a group convertible thereto, and R.sub.3 " is an electron withdrawing group, with a source of nitrous acid and thereafter converting the resulting .dbd.NOH group to .dbd.NR.sub.2 and converting R.sub.1 ' and R.sub.3 " when other than R.sub.1 and R.sub.3 to R.sub.1 and R.sub.3, wherein R.sub.1, R.sub.2 and R.sub.3 are as defined in formula (I); or ##STR7##
wherein R.sub.2 ' and R.sub.3 ' are R.sub.2 and R.sub.3 or groups convertible thereto and thereafter converting R.sub.2 ' and R.sub.3 ' when other than R.sub.2 and R.sub.3 to R.sub.2 and R.sub.3 as defined in

REFERENCES:
patent: 5278170 (1994-01-01), Orlek et al.

Affiliated with

Also associated with

Rating

Derivatives of quinuclidine n-oxide as muscarinic receptor ligan does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Derivatives of quinuclidine n-oxide as muscarinic receptor ligan, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Derivatives of quinuclidine n-oxide as muscarinic receptor ligan will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2358443