Substituted indole acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
申请人:Wyeth
公开号:US20030125371A1
公开(公告)日:2003-07-03
This invention provides compounds of the formula:
1
wherein: X is a chemical bond, —CH
2
— or —C(O)—; R
1
is alkyl, cycloalkyl, —CH
2
-cycloalkyl, pyridinyl, —CH
2
-pyridinyl, phenyl or benzyl; R
2
is H, alkyl, cycloalkyl, —CH
2
-cycloalkyl, or perfluoroalkyl; R
3
is H, halo, alkyl, perfluoroalkyl, alkoxy, cycloalkyl, —CH
2
-cycloalkyl, —NH
2
, or —NO
2
; R
4
is optionally substituted phenyl, benzyl, benzyloxy, pyridinyl, or —CH
2
-pyridinyl, or the salt or ester forms thereof, as well as methods for using the compounds as inhibitors of plasminogen activator inhibitor-1 (PAI-1) and as therapeutic compositions for treating conditions resulting from fibrinolytic disorders such as deep vein thrombosis and coronary heart disease, and pulmonary fibrosis.
这项发明提供了以下结构的化合物:其中:X是化学键,-CH2-或-C(O)-;R1是烷基、环烷基、-CH2-环烷基、吡啶基、-CH2-吡啶基、苯基或苄基;R2是H、烷基、环烷基、-CH2-环烷基或全氟烷基;R3是H、卤素、烷基、全氟烷基、烷氧基、环烷基、-CH2-环烷基、-NH2或-NO2;R4是可选择地取代的苯基、苄基、苄氧基、吡啶基或-CH2-吡啶基,或其盐或酯形式,以及使用这些化合物作为纤溶酶原激活抑制剂-1(PAI-1)的抑制剂和作为治疗配方,用于治疗由纤溶障碍引起的疾病,如深静脉血栓形成、冠心病和肺纤维化。