Bioorg Med Chem Lett 2019 Jun 3;29(12):1541-1545. Epub 2019 Apr 3.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. Electronic address:
Introducing purine bases to P2-ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitory because of the carbonyl and NH groups promoting the formation of extensive H-bonding interactions. In this work, thirty-three compounds are synthesized and evaluated, among which inhibitors 16a, 16f and 16j containing N-2-(6-substituted-9H-purin-9-yl)acetamide as the P2-ligands along with 4-methoxylphenylsulfonamide as the P2'-ligand, display potent inhibitory effect on the activity of HIV-1 protease with IC 43 nM, 42 nM and 68 nM in vitro, respectively.