Antiplatelet activity of nipecotamides in experimental thrombosis in mice.
Antiplatelet activity of nipecotamides in experimental thrombosis in mice.
复制标题
尼培酰胺在小鼠实验性血栓形成中的抗血小板活性。
DOI：
10.1002/jps.2600830222
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发表时间：
1994
影响因子：
3.8
通讯作者：
Gollamudi,R
中科院分区：
文献类型：
--
作者：
Lawrence,WH;Howell,RD;Gollamudi,R
□设计、合成了一组哌啶酰胺类化合物（3-氨基甲酰基哌啶），并评价了它们对诱导的血小板聚集的保护能力。采用小鼠血栓形成模型，观察这些化合物对静脉注射胶原蛋白加肾上腺素引起的血栓性猝死的保护作用。对映体选择性在决定这些化合物的活性中起着关键作用。亲脂性，而以前发现的相关性以及内vitroactivity，并没有直接invivoactivity的影响。哌啶环3位上酰胺官能团的存在对活性是必不可少的。在本文报道的10种化合物中，α，α ′-双[3-（N-苄基-N-甲基氨基甲酰基）-对二甲苯二氢溴酸盐（4）在预防小鼠诱导的血管内血小板聚集方面最有效，其半数有效剂量（ED_（50））为27.5 μmol（20 mg）/kg。
□ A group of nipecotamides (3-carbamoylpiperidines) were designed, synthesized, and evaluated for their ability to protect platelets from induced aggregation. Anin vivomouse thrombosis model was used to determine the protection afforded by these compounds from sudden thrombotic death induced by intravenous collagen plus epinephrine. Enantioselectivity appears to play a pivotal role In determining the activity of these compounds. Lipophilicity, whereas previously found to correlate well within vitroactivity, did not directly influencein vivoactivity. The presence of an amide function on the 3-posltlon of the piperidine ring was essential for activity. Of the 10 compounds reported here, α,α’-bis[3-(N-benzyl-N-methylcarbamoyl)- plperldlno]-p-xylene dlhydrobromide (4) was the most potent in preventing Induced intravascular platelet aggregation in mice, with a 50% effective dose of (ED50) of 27.5 μmol (20 mg)/kg.