Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1990-04-27
1993-04-13
Rotman, Alan L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
546 80, 546 81, 546 82, 546 83, 546 84, 546 93, 546104, 514291, C07D491052, A61K 3144
Patent
active
052024407
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to 4-aminopyridine derivatives. The compounds of the present invention inhibit brain acetylcholinesterase and are useful in the treatment of Alzheimer's disease.
Tetrahydroaminoacridine, which has anticholinesterase activity, has been reported to produce improved performance in psychological tests in patients afflicted with Alzheimer's disease (W. K. Summers et al., The New England Journal of Medicine, 315, 1241-1245 (1986)). The anticholinesterase physostigmine has also been reportedly used in the experimental treatment of Alzheimer's disease (S. D. Brinkman et al., Neurobiol. Aging, 4, 139-145 (1983)).
The compounds described in the following four documents are alleged to have anticholinesterase activity:
U.S. Pat. No. 4,652,567 refers to benzo(C)-1,5-naphthyridines for treating Alzheimer's disease.
U.S. Pat. No. 4,631,286 refers to 9-amino-1,2,3,4-tetrahydroacridine-1-ol and related compounds for treating Alzheimer's disease.
U.S. Pat. No. 4,550,113 refers to 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)quinoline monohydrate hydrochloride for treating neuritis, injuries of the peripheral nervous system, hereditary neuromuscular diseases, and disseminated sclerosis.
U.S. Pat. No. 4,578,394 refers to dihydropyridines for treating Alzheimer's disease.
U.S. Pat. No. 4,540,564 refers to dihydropyridines for delivering drugs to the brain.
G. K. Patnaik et al., J. Med. Chem., 9, 483-488 (1966), refer to 4-substituted 2,3-polymethylenequinolines having analgetic, local anesthetic, analeptic, and respiratory stimulant activities.
British Patent Specifications 1,186,061, 1,186,062, and 1,186,063 refer to benzonaphthyridine derivatives.
SUMMARY OF THE INVENTION
The present invention relates to compounds of the formula ##STR1## wherein A is selected from the group consisting of ##STR2## wherein one of the CH moieties at positions a, b, c and d of formula 1 may be replaced by a nitrogen atom or each of the CH moieties at positions a and d, a and c or b and d may be replaced by a nitrogen atom; B is selected from the group consisting of ##STR3## wherein each broken line represents an optional double bond; R.sup.1 is hydrogen or C.sub.1 -C.sub.6 alkyl; R.sup.3 is independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkanoyl, di(C.sub.1 -C.sub.6 alkylamino)-C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy-C.sub.1 -C.sub.6 alkyl, halogen (e.g., fluoro, chloro, bromo or iodo), hydroxy, nitro, phenyl, substituted phenyl, phenyl-C.sub.1 -C.sub.6 alkyl, substituted phenyl-C.sub.1 -C.sub.6 alkyl, diphenyl-C.sub.1 -C.sub.6 alkyl wherein one or both of the phenyl groups may be replaced with a substituted phenyl group, furyl-C.sub.1 -C.sub.6 alkyl, thienyl-C.sub.1 -C.sub.6 alkyl, phenyloxy, substituted phenyloxy, NHCOR.sup.5 and NR.sup.6 R.sup.7, wherein the phenyl moieties on the substituted phenyl and substituted phenylalkyl groups are substituted with one or more substituents (preferably, one or two substituents) selected from the group consisting of halogen (e.g., fluoro, chloro, bromo or iodo), C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy-C.sub.1 -C.sub.6 alkyl, hydroxy and nitro, and wherein R.sup.5, R.sup.6 and R.sup.7 are independently selected from C.sub.1 -C.sub.6 alkyl and C.sub.1 -C.sub.6 alkanoyl; R.sup.2 is independently selected from the group consisting of 1,4-dihydropyridyl-C.sub.1 -C.sub.6 alkanoyl, C.sub.1 -C.sub.6 alkyl-1,4-dihydropyridyl-C.sub.1 -C.sub.6 -alkanoyl, and the possible definitions set forth above for R.sup.3, except that R.sup.2 cannot be hydroxy, halogen, C.sub.1 -C.sub.6 alkoxy, phenyloxy or substituted phenyloxy; R.sup.4 is independently selected from the possible definitions set forth above for R.sup.3, except that R.sup.4 cannot be halogen, nitro, NHCOR.sup.5 or NR.sup.6 R.sup.7 ; n is 1, 2 or 3; Z.sup.1 is NH, O, S or NR.sup.8 wherein R.sup.8 is C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkanoyl; Z.sup.2 is O or S; Z.sup.3 are indepe
REFERENCES:
patent: 3232945 (1966-02-01), Sigal, Jr. et al.
patent: 3318896 (1967-05-01), Pribyl et al.
patent: 3541066 (1970-11-01), Wolf
patent: 3580915 (1971-05-01), Wolf et al.
patent: 4180580 (1979-12-01), Demerson et al.
patent: 4550113 (1985-10-01), Lavretskaya et al.
patent: 4578394 (1986-03-01), Allen et al.
patent: 4631286 (1986-12-01), Shutske et al.
patent: 4652567 (1987-03-01), Martin et al.
patent: 4680297 (1987-07-01), Blythin et al.
patent: 4680298 (1987-07-01), Blythin et al.
patent: 4695573 (1987-09-01), Shutske et al.
patent: 4753950 (1988-06-01), Shutske et al.
Indian Journal of Chemistry, vol. 26B Oct. 1987 pp. 910-913.
Chem. Abst. vol. 69 No. 25 Abst. No. 106408d, 1968.
Chem. Abstracts, vol. 92 No. 1, Abst. No. 6385a; Arne Osbirk et al., 1980.
Chem. Abstracts, vol. 108, Abst. No. 124385x, 1988.
Fedowich Valerie M.
Ginsburg Paul H.
Pfizer Inc.
Richardson Peter C.
Rotman Alan L.
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