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
1999-08-17
Gupta, Yogendra N.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514213, 514312, 514418, 514431, 514445, 514450, 514456, 540593, 546153, 546155, 549 12, 549 23, 549 28, 549 52, 549350, 549400, 549401, A61K 3137, A61K 3138, C07D31126, C07D33506
Patent
active
059394528
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, benzophenones, 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 ##STR2## 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; ##STR3## 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, --O(CH.sub.2).sub.q CHX.sup.9 X.sup.10, and --O(CH.sub.2).sub.q X.sup.10 ; phenyl; one 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; 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, phenylsulfonyl and optionally substituted 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;
R.sup.6 and R.sup.7 are each independently hydrogen or (C.sub.1 -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 (C.sub.4 -C.sub.7)cycloalkyl; or trans --(CH.sub.2).sub.m --CX.sup.1 .dbd.CX.sup.2 --CO.sub.2 H, --(CH.sub.2).sub.m CX.sup.3 X.sup.4 X.sup.5, --CO--NG.sup.1 G.sup.2, ##STR4## and a substituted five or six membered aromatic ring optionally having one or two heteroatoms where the heteroatoms are 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 (C.sub.3 -C.sub.7)cycloalkyl; independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6)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; 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; substituent selected from the group consisting
REFERENCES:
patent: 3953500 (1976-04-01), Shunsaku
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).
Lichtenberger, J. et al., Bulletin De La Societe Chimique de France, 1963, pp. 275-282, No. 47.
Aono, T. et al., Chemical & Pharmaceutical Bulletin, vol. 26, No. 5, May 1978, pp. 1511-1521.
Panetta, C. A. et al., Synthesis, No. 1, Jan. 1981, pp. 59-60.
Sarges, R. et al., J. Med. Chem., vol. 31, No. 1, Jan. 1988, pp. 230-243.
Horaguchi, T. et al., J. C. S., Chem. Comm., No. 1, Jan. 1991, pp. 44-46.
Duewell, H. et al., Australian J. of Chem., vol. 41, No. 4, 1988, pp. 535-548.
Bethune, R. J. et al., J. Chem. Soc., Perkin Transactions 1, No. 14, Jul. 1994, pp. 1925-1933.
Abraham, et al., Phytochemistry, 29(8), 2641-4 (1990).
Kano, et al., "An Intramolecular Rearrangement of 1-arylazetidin-2-ones in an Acidic Solution", Heterocycles, 4(10), pp. 1649-1653 (1976).
Merchant, et al., "Reactions of Nitriles. VIII. Synthesis of 2,3-Dihydro-4(1H)-Quinolinones", J. Chem. Soc., Perkins Trans, 1, (7), pp. 932-935 (1972).
Dombroski Mark Anthony
Koch Kevin
Piscopio Anthony Daniel
Appleman Jolene W.
Ginsburg Paul H.
Gupta Yogendra N.
Pfizer Inc
Richardson Peter C.
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