Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-04-09
2000-04-18
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514432, 549 23, 549399, 549400, 549401, 549402, 549403, C07D31156, C07D31122, C07D31158, A61K 31352
Patent
active
060516011
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to novel benzopyran and other benzo-fused leukotriene B.sub.4 (LTB.sub.4) antagonists, the pharmaceutically acceptable salts of said compounds, to pharmaceutical compositions containing such compounds, and to a method of using such compounds as LTB.sub.4 antagonists.
The compounds of this invention inhibit the action of LTB.sub.4 and are therefore useful in the treatment of LTB.sub.4 induced illnesses such as inflammatory disorders including rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, psoriasis and other skin disorders such as eczema, erythema, pruritus and acne, stroke and other forms of reperfusion injury, graft rejection, autoimmune diseases, asthma, and other conditions where marked neutrophil infiltration occurs.
Leukotriene B.sub.4 antagonists are disclosed in European patent publications 276 064 and 292 977 which refer to diphenylethers, benzcphenones, and other compounds containing two phenyl groups, and 7-(3-alkoxy-4-alkanoyl-phenoxy)alkoxy benzopyran derivatives, respectively.
SUMMARY OF THE INVENTION
The present invention is directed to novel benzopyran and other benzo-fused leukotriene B.sub.4 (LTB.sub.4) antagonist compounds, of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein A.sup.1 is O, CH.sub.2, S, NH or N(C.sub.1 -C.sub.6)alkyl; ##STR2## R.sup.4 is hydrogen or hydroxy; R.sup.5 is selected from the group consisting of --(CH.sub.2).sub.n CHX.sup.9 X.sup.10, --(CH.sub.2).sub.n X.sup.10 and --CH(OH)X.sup.10 ; phenyl; or two substituents independently selected from the group consisting of fluoro, chloro, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.4)perfluoroalkyl, (C.sub.1 -C.sub.4)perfluoroalkoxy, (C.sub.1 -C.sub.6)alkylthio, (C.sub.1 -C.sub.6)alkylsulfinyl, phenylsulfinyl, (C.sub.1 -C.sub.6)alkylsulfonyl and phenylsulfonyl; or one of the following optionally substituted rings: phenyl, thienyl, pyridyl, furyl, naphthyl, quinolyl, isoquinolyl, pyrimidinyl or pyrazinyl; two substituenis independently selected from the group consisting of fluoro, chloro, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C,)alkoxy, (C.sub.1 -C.sub.4)perfluoro-alkyl, (C.sub.1 -C.sub.4)perfluoroalkoxy, (C.sub.1 -C.sub.6)alkylthio, (C.sub.1 -C.sub.6)alkylsulfinyl, phenylsulfinyl, (C.sub.1 -C.sub.6)alkylsulfonyl, phenylsulfonyl and optionally substituted phenyl; two substituents independently selected from the group consisting of fluoro, chloro, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.4)perfluoroalkyl, (C.sub.1 -C.sub.4)perfluoroalkoxy, (C.sub.1 -C.sub.6)alkylthio, (C.sub.1 -C.sub.6)alkylsulfinyl, phenylsulfinyl, (C.sub.1 -C.sub.6)alkyl-sulfonyl and phenylsulfonyl; -C.sub.4)alkyl or R.sup.6 and R.sup.7 are taken together with the carbon atom to which they are attached and form a (C.sub.4 -C.sub.7)cycloalkyl; or trans ##STR3## and a substituted five or six membered aromatic ring optionally having one or two heteroatoms where the heteroatoms are optionally independently selected from the group consisting of O, S and N; -C.sub.6)alkyl; -C.sub.6)alkyl or X.sup.3 and X.sup.4 are taken together with the carbon atom to which they are attached and form a (C.sub.3 -C.sub.7)cycloalkyl; independently selected from the group consisting of hydrogen, (C.sub.1 -C;)alkyl, (C.sub.1 -C.sub.4)perfluoroalkyl, (C.sub.1 -C.sub.6)alkylsulfinyl, phenylsulfinyl, (C.sub.1 -C.sub.6)alkylsulfonyl, phenylsulfonyl, hydroxy, phenyl and (Q.sup.1).sub.a -substituted phenyl; (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)a koxy, (C.sub.1 -C,)perfluoroalkyl, (C.sub.1 -C.sub.4)perfluoroalkoxy, (C.sub.1 -C.sub.6)alkylthio, (C.sub.1 -C.sub.6)alkylsulfinyl, phenylsulfinyl, (C.sub.1 -C.sub.6)alkyl-sulfonyl and phenylsulfonyl; substituent selected from the group consisting of carboxy, tetrazolyl, --CO--N(H)(SO.sub.2 --X.sup.7), --N(H)(SO.sub.2 --X.sup.7), --N(H)(CO--X.sup.7), and --N(H)(CO--OX.sup.7) and by one or two substituents each independently selected from the group consisting of fluoro, chloro, (C.sub.1 -C.sub.
REFERENCES:
patent: 4565882 (1986-01-01), Miyano et al.
patent: 4996230 (1991-02-01), Gapinski
Djuric, S. W. et al., J. Med. Chem., 32(6), 1145-7, (1989).
Marder, P. et al., Prostaglandins Leukotrienes and Essential Fatty Acids (1992), 46, 265-270.
Pettipher, E. R. et al., Br. J. Pharmacol. (1993), 110, 423-427.
Harvath, L., J. Immunology, 139(9), 3055-3061, (1987).
Sherman, J. W., J. Immunology, 140 (11), 3900-3904, (1988).
Panetta, C. A. et al., Synthesis, No. 1, Jan. 1981, pp. 59-60.
Abraham, W. R. et al., Phytochemistry, vol. 29, No. 8, Aug. 1990, pp. 2641-2644.
Dombroski Mark Anthony
Koch Kevin
Piscopio Anthony Daniel
Appleman Jolene W.
Ginsburg Paul H.
Pfizer Inc.
Rao Deepak
Richardson Peter C.
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