Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-10-12
1997-11-18
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546 16, A61K 31445, C07D47110
Patent
active
056888066
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to novel spirocyclic piperidine derivatives and related compounds, 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 following references refer, collectively, to quinuclidine, piperidine, and azanorbornane derivatives and related compounds that exhibit activity as substance P receptor antagonists: U.S. Pat. No. 5,162,339, which issued on Nov. 11, 1992; 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 065337/92, filed Mar. 23, 1992; U.S. patent application Ser. No. 932,392, filed Aug. 19, 1992; and U.S. patent application Ser. No. 988,653, filed Dec. 10, 1992.
SUMMARY OF THE INVENTION
The present invention relates to compounds of the formula ##STR2## wherein Z is NH, O or CH.sub.2 ;
R.sup.l is phenyl optionally substituted with one or more substituents, preferably with from one to three substituents, independently selected from hydrogen, halo, nitro, (C.sub.1 -C.sub.10)alkyl optionally substituted with from one to three fluorine atoms, (C.sub.1 -C.sub.10)alkoxy optionally substituted with from one to three fluorine atoms, trifluoromethyl, hydroxy, phenyl, cyano, amino, (C.sub.1 -C.sub.6)-alkylamino, di-(C.sub.1 -C.sub.6)alkylamino, ##STR3## (C.sub.1 -C.sub.4)alkoxy(C.sub.1 -C.sub.4)alkyl, --S(O).sub.v -- (C.sub.1 -C.sub.10)-alkyl wherein v is zero, one or two, --S(O).sub.v -aryl wherein v is zero, one or two, --O-aryl, --SO.sub.2 NR.sup.9 R.sup.10 wherein each of R.sup.4 and R.sup.5 is, independently, (C.sub.1 -C.sub.6)alkyl, or R.sup.4 and R.sup.5, together with the nitrogen to which they are attached, form a saturated ring containing one nitrogen and from 3 to 6 carbons ##STR4## wherein one or both of the alkyl moieties may optionally be substituted with from one to three fluorine atoms, --N(SO.sub.2 -(C.sub.1 -C.sub.10)alkyl).sub.2 and ##STR5## and wherein the aryl moieties of said --S(O).sub. -aryl, --O-aryl and ##STR6## are independently selected from phenyl and benzyl and may optionally be substituted with from one to three substituents independently selected from (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy and halo;
or R.sup.1 is phenyl substituted with a group having the formula ##STR7## wherein a is 0, 1 or 2 and the asterisk represents a position meta to the point of attachment of R.sup.1 ;
R.sup.2 is selected from (C.sub.1 -C.sub.6) straight or branched alkyl, (C.sub.3 -C.sub.7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; aryl selected from biphenyl, phenyl, indanyl and naphthyl; heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxaz
REFERENCES:
patent: 4804665 (1989-02-01), Goto et al.
patent: 4940795 (1990-07-01), Tsukamoto et al.
patent: 5075317 (1991-12-01), Wu et al.
patent: 5162339 (1992-11-01), Lowe, III
patent: 5373003 (1994-12-01), Lowe, III
patent: 5393762 (1995-02-01), Desai et al.
Maggi, C.A. et al, J. Auton. Pharmacol. 1993, 13, pp. 23-93.
Desai Manoj C.
Vincent Lawrence A.
Dahlen Garth M.
DeBenedictis Karen
Ginsburg Paul H.
Ivy C. Warren
Pfizer Inc.
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