申请人:Zeneca Limited
公开号:US05420298A1
公开(公告)日:1995-05-30
The invention concerns pyrrolidine derivatives of the formula ##STR1## wherein Ar.sup.1 is optionally-substituted phenyl, naphthyl or a 10-membered bicyclic heterocyclic moiety containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulphur; A is a direct link to the group X or A is (1-4C)alkylene; X is oxy, thio, sulphinyl or sulphonyl; Ar.sup.2 is phenylene, pyridinediyl, pyrimidinediyl, thiophendiyl, furandiyl or thiazolediyl; R.sup.1 is (1-4C)alkyl, (3-4C)alkenyl or (3-4C)alkynyl; R.sup.2 is (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, halogeno-(1-4C)alkyl, halogeno-(2-4C)alkenyl, halogeno-(2-4C)alkynyl, (1-4C)alkoxy-(2-4C)alkyl, hydroxy-(2-4C)alkyl, cyano-(1-4C)alkyl, carboxy-(1-4C)alkyl, carbamoyl-(1-4C)alkyl, (1-4C)alkoxycarbonyl-(1-4C)alkyl, N-(1-4C)alkylcarbamoyl-(1-4C)alkyl or N,N-di-(1-4C)alkylcarbamoyl-(1-4C)alkyl; and n is 1 or 2 and each R.sup.3 is independently hydrogen, hydroxy, (1-4C)alkyl or (1-4C)alkoxy; or a pharmaceutically-acceptable salt thereof; processes for their manufacture; pharmaceutical compositions containing them and their use as 5-lipoxygenase inhibitors.
该发明涉及以下结构的吡咯烷衍生物:其中Ar.sup.1是可选择取代的苯基、萘基或含有一个或两个氮杂原子的10元杂环基团,且可选择地含有来自氮、氧和硫的进一步杂原子;A是直接连接到基团X的链或A是(1-4C)烷基链;X是氧、硫、亚硫酰基或磺酰基;Ar.sup.2是苯基、吡啶二基、嘧啶二基、噻吩二基、呋喃二基或噻唑二基;R.sup.1是(1-4C)烷基、(3-4C)烯基或(3-4C)炔基;R.sup.2是(1-4C)烷基、(2-4C)烯基、(2-4C)炔基、卤代-(1-4C)烷基、卤代-(2-4C)烯基、卤代-(2-4C)炔基、(1-4C)烷氧基-(2-4C)烷基、羟基-(2-4C)烷基、氰基-(1-4C)烷基、羧基-(1-4C)烷基、氨基甲酰基-(1-4C)烷基、(1-4C)烷氧羰基-(1-4C)烷基、N-(1-4C)烷基氨基甲酰基-(1-4C)烷基或N,N-二-(1-4C)烷基氨基甲酰基-(1-4C)烷基;n为1或2,每个R.sup.3独立地是氢、羟基、(1-4C)烷基或(1-4C)烷氧基;或其药学上可接受的盐;其制备方法;含有它们的药物组合物以及它们作为5-脂氧合酶抑制剂的用途。