Rynbrandt R H, Nishizawa E E, Balogoyen D P, Mendoza A R, Annis K A
J Med Chem. 1981 Dec;24(12):1507-10. doi: 10.1021/jm00144a026.
In our continuing effort to discover compound which inhibit collagen-induced platelet aggregation, we have screened compounds in a mouse pulmonary thromboembolism screen. Methyl 4,5-bis(4-methoxyphenyl)-2-thiazoleacetate (3) was very active in the above screen. However, 3 was active for less than 5 min when given orally to guinea pigs. As a result, our synthetic goal was to prepare 2-substituted thiazoles with a much longer duration of activity. This paper describes the preparation of a number 4,5-bis(aryl)-2-substituted-thiazoles and their in vitro and ex vivo activity against collagen-induced platelet aggregation. It was determined that 4,5-bis(4-methoxyphenyl)-2-(trifluoromethyl)thiazole (16) is the most promising compound.
在我们持续不断地发现抑制胶原诱导血小板聚集化合物的过程中，我们在小鼠肺血栓栓塞模型中对化合物进行了筛选。4,5-双(4-甲氧基苯基)-2-噻唑乙酸甲酯(3)在上述筛选中表现出很高的活性。然而，给豚鼠口服3时，其活性持续不到5分钟。因此，我们的合成目标是制备活性持续时间长得多的2-取代噻唑。本文描述了一系列4,5-双(芳基)-2-取代噻唑的制备及其对胶原诱导血小板聚集的体外和体内活性。已确定4,5-双(4-甲氧基苯基)-2-(三氟甲基)噻唑(16)是最有前景的化合物。
