Novel inhibitors of HIV protease: design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds

  • Bioorg Med Chem Lett. 2000 Jun 5;10(11):1159-62.
A Spaltenstein  1 ,  M R Almond ,  W J Bock ,  D G Cleary ,  E S Furfine ,  R J Hazen ,  W M Kazmierski ,  F G Salituro ,  R D Tung ,  L L Wright
Affiliations
PMID: 10866371
Abstract

A novel series of HIV Protease Inhibitors containing cyclic P1/P2 scaffolds has been synthesized and evaluated for biological activity. The trans 3,5-dibenzyl-2-oxo pyrrolidinone ring system resulted in a 50 pM enzyme inhibitor against HIV Protease in vitro when combined with an indanolamine derived P'-backbone. This compound also shows comparable activity to currently marketed drugs in the MT-4 cell-based Antiviral assay.