Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-06-19
1999-03-23
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546133, A61K 31435, C07D45302
Patent
active
058860096
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to the novel quinuclidine derivatives (2S,3S)-N-(5-n-propyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo and the use of such compound in the treatment and prevention of inflammatory and central nervous system disorders, as well as several other disorders. The pharmaceutically active compound of this invention is a substance P receptor antagonists.
Substance P is a naturally occurring undecapeptide belonging to the tachykinin family of peptides, the latter being named because of their prompt stimulatory action on smooth muscle tissue. More specifically, substance P is a pharmacologically active neuropeptide that is produced in mammals (having originally been isolated from gut) and possesses a characteristic amino acid sequence that is illustrated by D. F. Veber et al. in U.S. Pat. No. 4,680,283. The wide involvement of substance P and other tachykinins in the pathophysiology of numerous diseases has been amply demonstrated in the art. For instance, substance P has recently been shown to be involved in the transmission of pain or migraine (see B. E. B. Sandberg et al., Journal of Medicinal Chemistry, 25, 1009 (1982)), as well as in central nervous system disorders such as anxiety and schizophrenia, in respiratory and inflammatory diseases such as asthma and rheumatoid arthritis, respectively, in rheumatic diseases such as fibrositis, and in gastrointestinal disorders and diseases of the GI tract such as ulcerative colitis and Crohn's disease, etc. (see D. Regoli in "Trends in Cluster Headache," edited by F. Sicuteri et al., Elsevier Scientific Publishers, Amsterdam, pp. 85-95 (1987)).
The quinuclidine derivative of this invention is referred to generically in U.S. Pat. No. 5,162,339, which issued to John A. Lowe III on Nov. 11, 1992.
Quinuclidine, piperidine, and azanorbornane derivatives and related compounds that exhibit activity as substance P receptor antagonists are referred to in U.S. patent application Ser. No. 724,268, filed Jul. 1, 1991, PCT Patent Application PCT/US 91/02853, filed Apr. 25, 1991, PCT Patent Application PCT/US 91/03369, filed May 14, 1991, PCT Patent Application PCT/US 91/05776, filed Aug. 20, 1991, PCT Patent Application PCT/US 92/00113, filed Jan. 17, 1992, PCT Patent Application PCT/US 92/03571, filed May 5, 1992, PCT Patent Application PCT/US 92/03317, filed Apr. 28, 1992, PCT Patent Application PCT/US 92/04697, filed Jun. 11, 1992, U.S. patent application Ser. No. 766,488, filed Sep. 26, 1991, U.S. patent application Ser. No. 790,934, filed Nov. 12, 1991, PCT Patent Application PCT/US 92/04002, filed May 19, 1992, Japanese Patent Application No. 065337/92, filed Mar. 23, 1992, and U.S. patent application Ser. No. 932,392, filed Aug. 19, 1992.
SUMMARY OF THE INVENTION
The present invention relates to the quinuclidine derivative (2S,3S)-N-(5-n-propyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo 2.2.2!octan-3-amine has the following chemical structure ##STR1##
The present invention also relates to a pharmaceutical composition for treating or preventing a condition selected from the group consisting of inflammatory diseases (e.g., arthritis, psoriasis, asthma and inflammatory bowel disease), anxiety, depression or dysthymic disorders, colitis, psychosis, pain, allergies such as eczema and rhinitis, chronic obstructive airways disease, hypersensitivity disorders such as poison ivy, hypertension, vasospastic diseases such as angina, migraine and Reynaud's disease, fibrosing and collagen diseases such as scleroderma and eosinophilic fascioliasis, reflex sympathetic dystrophy such as shoulder/hand syndrome, addiction disorders such as alcoholism, stress related somatic disorders, peripheral neuropathy, neuralgia, neuropathological disorders such as Alzheimer's disease, AIDS related dementia, diabetic neuropathy and multiple sclerosis, disorders related to immune enhancement or suppression such as systemic lupus erythematosus, and rheumatic diseases such as fibrositis in a mammal, including a human, comprising
REFERENCES:
patent: 5360820 (1994-11-01), Hagan
patent: 5451586 (1995-09-01), Lowe
patent: 5519033 (1996-05-01), Rosen
Parnet, P. et al., Abstract from Gastro-Enterologica Belgica., Supplement, 1993, p. 64.
Blaser, M.J., Gastroenterology, 1992, 102, pp. 720-727.
Beding-Barnekow, B. et al., Br. J. Pharmcol. 1988,95(1), pp. 259-267.
Holmdahl, G. et al., Science, 1981, 214(4524), pp. 1029-1031.
Krupin, T. et al., Exp. Eye, Res., 1982, 34(3), pp. 319-324.
Tiseo, P.J. et al., CIBA Foundation Symposium, 1990, 151, pp. 91-104.
Merck Manual, edited by Berkow et al., 16th ed., 1992, Merck Research Labs, pp. 306, 815-816, 1308-1312, 1582-1583, 1603-1614, and 1635.
Ito Fumitaka
Kondo Hiroshi
Nakane Masami
Shimada Kaoru
Aulakh Charanjit S.
DeBenedictis Karen
Ginsburg Paul H.
Pfizer Inc.
Richardson Peter C.
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