Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1993-04-05
1994-10-18
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514357, 546 14, 546326, 546330, 546331, 546332, 546335, 546336, 546337, 546338, C07D21389, A61K 3144
Patent
active
053569148
DESCRIPTION:
BRIEF SUMMARY
This invention relates to compounds having pharmaceutical activity, to a process for their preparation and their use as pharmaceuticals.
EP-0288394, U.S. Pat. Nos. 4,921,868 and 4,902,699 disclose certain 1,2,5,6-tetrahydropyridine 3-ketoxime and -3-aldoxime derivatives having cholinomimetic activity.
A novel group of compounds has now been discovered which enhance acetylcholine function via an action at muscarinic receptors within the central nervous system and are 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: ##STR2## wherein R.sub.1 represents a 1,2,5,6-tetrahydropyridin-3-yl group N-substituted by R.sub.10 wherein R.sub.10 represents OH; a group hydrolysable in vivo to OH or hydrogen; C.sub.1-8 alkoxy; C.sub.2-8 alkenyloxy; C.sub.2-8 alkynyloxy; C.sub.3-8 cycloalkyloxy; or COR.sub.13 wherein R.sub.13 represents hydrogen, C.sub.1-8 alkyl, phenyl or phenyl C.sub.1-4 alkyl; in which any phenyl moiety is optionally substituted by up to 3 substitutents independently selected from C.sub.1-6 alkoxy, C.sub.1-6 alkyl, halo, C.sub.1-6 alkoxycarbonyl, cyano, C.sub.1-6 alkylthio or C.sub.1-6 alkylsulphonyl;
R.sub.2 is a group OR.sub.4, where R.sub.4 is C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, a group OCOR.sub.5 where R.sub.5 is hydrogen or R.sub.4, or a group NHR.sub.6 or NR.sub.7 R.sub.8 where R.sub.6, R.sub.7 and R.sub.8 are independently C.sub.1-2 alkyl; and
R.sub.3 is chloro, fluoro, bromo, C.sub.1-3 alkyl substituted by one, two or three halogen atoms, or R.sub.3 is a group (CH.sub.2).sub.n R.sub.9 where R.sub.9 is --CN, --OH, --OCH.sub.3, --SH or --SCH.sub.3 and n is O or 1, with the proviso that when n is O, R.sub.9 is not --OH or --SH.
The term halogen includes bromine, chlorine, fluorine and iodine. R.sub.3 halo is preferably fluorine. Halo in R.sub.10 is preferably chlorine.
Compounds of formula (I) are capable of existing in a number of stereoisomeric forms including geometric isomers such as syn and anti and, for certain compounds, 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 compounds of formula (I) can form acid addition salts with acids, such as the conventional pharmaceutically acceptable acids, for example hydrochloric, hydrobromic, phosphoric, acetic, fumaric, salicylic, citric, lactic, mandelic, tartaric, oxalic and methanesulphonic.
The term pharmaceutically acceptable salt encompasses solvates and hydrates. Thus where compounds of formula (I) or pharmaceutically acceptable salts thereof form solvates or hydrates, these also form an aspect of the invention.
Examples of suitable groups hydrolysable in vivo to OH include C.sub.1-8 alkanoyloxy, C.sub.1-8 alkoxycarbonyloxy, phenyl C.sub.1-4 alkanoyloxy and --OCONHR.sub.12 wherein R.sub.12 is hydrogen, C.sub.1-8 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, C.sub.3-8 cycloalkyl, phenyl or phenyl C.sub.1-4 alkyl, in which any phenyl moiety is optionally substituted as aforesaid.
Examples of suitable groups hydrolysable in vivo to hydrogen include COOZ in which Z represents C.sub.1-18 alkyl optionally substituted by tri C.sub.1-6 alkylsilyl or C.sub.1-6 alkylsulphonyl, C.sub.2-18 alkenyl, C.sub.2-18 alkynyl, C.sub.3-8 cycloalkyl C.sub.1-4 alkyl, C.sub.3-10 cycloalkyl, phenyl or phenyl C.sub.1-4 alkyl; in which any phenyl moiety is optionally substituted as aforesaid.
In a preferred aspect, therefore, R.sub.10 represents COOZ in which Z represents C.sub.1-18 alkyl optionally substituted by tri C.sub.1-6 alkylsilyl or C.sub.1-6 alkylsulphonyl, C.sub.2-18 alkenyl, C.sub.2-18 alkynyl, C.sub.3-8 cycloalkyl C.sub.1-4 alkyl, C.sub.3-10 cycloalkyl, phenyl or phenyl C.sub.1-4 alkyl; OR.sub.11 wherein R.sub.11 represents hydrogen, C.sub
REFERENCES:
patent: 4710508 (1987-12-01), Bergmeier et al.
patent: 4786648 (1988-11-01), Bergmeier et al.
patent: 4798841 (1989-01-01), Downs
patent: 4927837 (1990-05-01), Galliani et al.
patent: 4937239 (1990-06-01), Lauffer et al.
patent: 5015655 (1991-05-01), Galliani et al.
patent: 5110828 (1992-05-01), Bromidge et al.
Bromidge Steven M.
Dabbs Steven
Orlek Barry S.
Beecham Group p.l.c.
Davis Zinna N.
Hall Linda E.
Ivy C. Warren
Lentz Edward T.
LandOfFree
1,2,5,6-tetrahydropyridine oxime derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 1,2,5,6-tetrahydropyridine oxime derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 1,2,5,6-tetrahydropyridine oxime derivatives will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2372770