Add time:08/13/2019 Source:sciencedirect.com
The structure–activity relationship of HIV-1 protease (HIV-1 PR) inhibitors containing α-hydroxy-β-amino acids is discussed. We demonstrated that substituent groups on the P1 aromatic rings of the inhibitors exert significant influence on their biological activity. Inhibitors bearing an alkyl or a fluorine atom at the meta and para position on their P1 benzene ring were found to be good inhibitors. We also discovered that the substitution positions of the P2 benzamides were crucial for good antiviral potency. In this study, inhibitor 48 was the most potent {IC90 (CEM/HIV-1 IIIB) 27 nM} and showed good pharmacokinetics in rats.
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