优化具有口服生物利用度的烷基胺肾素抑制剂。
Optimization of orally bioavailable alkyl amine renin inhibitors.
机构信息
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
出版信息
Bioorg Med Chem Lett. 2010 Jan 15;20(2):694-9. doi: 10.1016/j.bmcl.2009.11.066. Epub 2009 Dec 1.
PMID:19959358
Abstract
Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC(50) of 0.83nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10mg/kg resulted in >20h reduction of blood pressure in a double transgenic rat model of hypertension.
摘要
基于结构的药物设计导致了新型的烷基胺肾素抑制剂，其体外和体内效力得到了改善。先导化合物 21a 对人血浆肾素（PRA）的抑制作用的 IC50 为 0.83nM。在高血压的双转基因大鼠模型中，以 10mg/kg 的剂量口服给予 21a 可使血压降低超过 20 小时。
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