New pyridine alkanoic or alkenoic acid derivs. - useful as leukotriene B4 antagonists, esp. antiinflammatory, antiallergic and anti-proliferative agents.

摘要

Pyridine alkanoic or alkenoic acid derivs. of formula (I) and their salts are new. In (I), the dotted line denotes an optional bond; m,n,p and r = 0-5; q = 1 or 2; U = a single bond, CH2CH2, CHOH, CO, CH=CH, C=C, COCO or CHOH-CHOH; A = a single bond, phenylene or pyridinediyl; W = H, halogen, 1-4C alkyl, CF3, alkylsulphonylamino, NHSO2CF3, amylsulphonylaminocarbonyl, opt. esterified or amidated COOH, or OH; X = opt. esterified or amidated COOH; Y = O or CH2; Z = (a) a single bond when q = 2 or (b) 1-3C alkyl, 2-8C alkenyl, Ar, OAr or CH=CHAr when q = 1; Ar = phenyl opt. substd. by 1-4C alkyl, 1-4C alkoxy, 1-4C alkanoyl, halogen and/or CF3. USE - (I) are leukotriene B4 (LTB4) antagonists useful as antiinflammatory, antiallergic and antiproliferative agents for treating skin disorders, asthma, hayfever, colitis, multiple sclerosis, shock, leukaemia, atherosclerosis, etc. In an example, a soln. of 300 mg methyl 3-(3-hydroxy-2-pyridyl)-propionate and 450 mg (1E)-6-bromo-1-(4-methoxyphenyl)-1-hexene and 6ml DMF was treated with 1.02g Cs2CO3, stirred at room temp. under argon for 20 hr., and worked up to give 280mg (Ia) methyl ester. This (130mg) was stirred with 6.5ml of 2N NaOH in 6ml MeOH at room temp. for 20 hr. to give 107mg (Ia).