Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-05-07
1997-12-30
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514210, 514212, 514256, 514269, 514318, 514326, 514383, 514362, 514363, 514364, 514369, 514370, 514372, 514376, 514377, 514380, 514384, 514398, 514422, 540480, 540481, 540605, 544298, 544333, 546194, 546208, 546209, 546210, 546213, 5462764, 548127, 548128, 548129, 548130, 548135, 548 13, 548138, 548141, 548132, 548133, 548143, 548144, 548145, 548225, 548226, 548223, 548243, 548245, 548255, 5482632, 5482648, 548183, 548189, 548199, 548206, 548213, 548214, 548518, C07D21156, C07D27742, C07D41712, A61K 31425
Patent
active
057030650
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to novel heteroarylamino and heteroarylsulfonamido substituted 3-benzylaminomethylpiperidines substituted benzylamino nitrogen containing non-aromatic heterocycles, pharmaceutical compositions comprising such compounds and the use of such compounds in the treatment and prevention of inflammatory and central nervous system disorders, as well as several other disorders. The pharmaceutically active compounds of this invention are substance P receptor antagonists. This invention also relates to novel intermediates used in the synthesis of such 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 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 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)).
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. 566,338 filed Nov. 20, 1989, 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 compounds of the formula ##STR2## wherein ring A is an aryl group selected from phenyl, naphthyl, thienyl, dihydroquinolinyl and indolinyl, and wherein the --CH.sub.2 PR.sup.3 sidechain is attached to a carbon atom of ring A; ##STR3## wherein the point of attachment of said ##STR4## to ring A is the nitrogen atom and the point of attachment to R.sup.1 is the sulfur atom; (C.sub.1 -C.sub.6)alkoxy optionally substituted with from one to three fluorine atoms; three heteroatoms selected from sulfur, nitrogen and oxygen (e.g., thiazolyl, pyrrolyl, thienyl, triazolyl, oxazolyl, oxadiazolyl, thiadiazolyl or imidazolyl), wherein said heterocyclic ring may optionally be substituted with from one to three substituents, preferably with from zero to two substituents, independently selected from phenyl, (C.sub.1 -C.sub.6)alkyl optionally substituted with from one to three fluorine atoms, (C.sub.1 -C.sub.6)alkoxy optionally substituted with from one to three fluorine atoms and halo; ##STR5## wherein R.sup.6 and R.sup.10 are independently selected from furyl, thienyl, pyridyl, indolyl, biphenyl and phenyl, wherein said phenyl may optionally be substi
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Ginsburg Paul H.
Pfizer Inc.
Rao Deepak R.
Richardson Peter C.
Shah Mukund J.
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