阿利吉仑调研报告2011-6-7.pptVIP

The development of Aliskiren Zhao Fei 2011.06.08 Drawbacks of peptide-derived peptidomimetics 1、poor intestinal absorption 2、high liver first-pass metabolic inactivation 3、low oral bioavailability 4、synthetic complexity 5、high clinically effective doses 6、tolerance of patients（injection） In Vitro Activity of Renin Inhibitors with Methyl versus i-Propyl Moiety R3= R4= J. Med. Chem. 2007, 50, 4832-4844 optimization of R4 J. Med. Chem. 2007, 50, 4832-4844 J. Med. Chem. 2007, 50, 4832-4844 R4 * * 1，Aliskiren, the first marketed direct renin inhibitor (DRI) in 2007, Novartis 肾素-血管紧张素-醛固酮系统RAAS 肾素前体