公开(公告)号：US06248743B1

公开(公告)日：2001-06-19

申请号：US09143358

申请日：1998-08-28

申请人： Hiroshi Ohmizu ,  Akio Ohtani ,  Tsuyoshi Ohgiku ,  Hiroshi Sai ,  Jun Murakami

发明人： Hiroshi Ohmizu ,  Akio Ohtani ,  Tsuyoshi Ohgiku ,  Hiroshi Sai ,  Jun Murakami

IPC分类号： A61K31495

CPC分类号： C07D207/02 ,  C07C69/734 ,  C07C235/34 ,  C07C2601/08 ,  C07D211/58 ,  C07D213/40 ,  C07D213/55 ,  C07D213/56 ,  C07D213/75 ,  C07D213/89 ,  C07D231/12 ,  C07D231/38 ,  C07D231/40 ,  C07D233/56 ,  C07D239/42 ,  C07D249/08 ,  C07D261/14 ,  C07D317/60 ,  C07D401/06 ,  C07D405/12

摘要： A novel butadiene derivative of the formula: wherein Ring A is heterocycle, or benzene being optionally substituted by lower alkyl, alkoxy, nitro, hydroxy, substituted or unsubstituted amino or halogen, Ring B is heterocycle, or benzene being optionally substituted by lower alkoxy, lower alkylenedioxy or di-lower alkylamino, R1 and R2 are each H or lower alkyl, one of —COR32 and —COR42 is carboxyl, and the other is carboxyl being optionally esterified, or the corresponding amide or pyrrolidine derivatives, or a pharmaceutically acceptable salt thereof. Said compounds show excellent PAI-1 inhibitory activity and are useful in the prophylaxis or treatment of various thromboses such as myocardial infarction, intra-atrial thrombus in atrial fibrillation, cerebral infarction, angina pectoris, stroke, pulmonary infarction, deep venous thrombus (DVT), disseminated intravascular coagulation syndrome (DIC), diabetic complications, restenosis after percutaneous transluminal coronary angioplasty (PTCA), etc.

摘要翻译： 一种下式的新型丁二烯衍生物：其中环A是杂环，或任选被低级烷基，烷氧基，硝基，羟基，取代或未取代的氨基或卤素取代的苯，环B是杂环，或任选被低级烷氧基取代的苯， 低级亚烷基二氧基或二低级烷基氨基，R 1和R 2各自为H或低级烷基，-COR 32和-COR 42中的一个为羧基，另一个为任选被酯化的羧基，或相应的酰胺或吡咯烷衍生物或其药学上可接受的盐 其中。 所述化合物显示优异的PAI-1抑制活性，可用于预防或治疗心肌梗死，心房颤动，脑梗死，心绞痛，中风，肺梗死，深静脉血栓（DVT）等心血管栓塞， ，弥漫性血管内凝血综合征（DIC），糖尿病并发症，经皮腔内冠状动脉成形术（PTCA）后再狭窄等。