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Optimization of orally bioavailable alkyl amine renin inhibitors |
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| Authors: | Zhenrong Xu Salvacion Cacatian Jing Yuan Robert D Simpson Lanqi Jia Wei Zhao Colin M Tice Patrick T Flaherty Joan Guo Alexey Ishchenko Suresh B Singh Zhongren Wu Brian M McKeever Boyd B Scott Yuri Bukhtiyarov Jennifer Berbaum Jennifer Mason Reshma Panemangalore Maria Grazia Cappiello Ross Bentley David A Claremon |
| Institution: | 1. Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA;2. GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA |
| Abstract: | Structure-guided drug design led to new alkylamine renin inhibitors with improved in vitro and in vivo potency. Lead compound 21a, has an IC50 of 0.83 nM for the inhibition of human renin in plasma (PRA). Oral administration of 21a at 10 mg/kg resulted in >20 h reduction of blood pressure in a double transgenic rat model of hypertension. |
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