Abstract
A systematic investigation of the S 3 sub-pocket activity requirements was conducted. It was observed that linear and sterically small side chain substituents are preferred in the S 3 sub-pocket for optimal renin inhibition. Polar groups in the S 3-sub-pocket were not well tolerated and caused a reduction in renin inhibitory activity. Further, compounds with c log P’s ⩽ 3 demonstrated a dramatic reduction in CYP3A4 inhibitory activity.
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