Novel nonpeptide small molecule renin inhibitors bearing an N-isopropyl Pb>1b> motif were designed based on initial lead structures 1 and aliskiren (2). (Pb>3b>–Pb>1b>)-Benzamide derivatives such as 9a and 34, as well as the corresponding Pb>1b> basic tertiary amine derivatives 10 and 35 were found to display low nanomolar inhibition against human renin in vitro.