BENZOPYRAN AND BENZO-FUSED COMPOUNDS, THEIR PREPARATION AND THEIR USE AS LEUKOTRIENE B4' (LTB4) ANTAGONISTS

摘要

This invention relates to novel benzopyran and other benzo-fused leukotriene B4 (LTB4) antagonists of formula (I), and the pharmaceutically acceptable salts thereof wherein A<1> is O, CH2, S, NH or N(C1-C6)alkyl; A<2> is (a), (b) or (c); R<1> is selected from the group consisting of tetrazolyl, carboxyl, cis or trans -(CH2)m-CX<1> = CX<2>-CO2H, -(CH2)mCX<3>X<4>X<5>, -CO-NG<1>G<2>, (d), 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; R<2> is hydrogen, fluoro, chloro, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C4)perfluoroalkyl, (C1-C4)perfluoroalkoxy, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, phenylsulfinyl, (C1-C6)alkylsulfonyl or phenylsulfonyl; and to the corresponding intermediates of formula (1A), and to pharmaceutical compositions containing such compounds, and to a method of using such compounds as LTB4 antagonists. The compounds of this invention inhibit the action of LTB4 and are therefore useful in the treatment of LTB4 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.