Design and synthesis of potent macrocyclic HIV-1 protease inhibitors involving P1-P2 ligands.

ABSTRACT: A series of potent macrocyclic HIV-1 protease inhibitors have been designed and synthesized. The compounds incorporated 16- to 19-membered macrocyclic rings between a nelfinavir-like P2 ligand and a tyrosine side chain containing a hydroxyethylamine sulfonamide isostere. All cyclic inhibitors are more potent than their corresponding acyclic counterparts. Saturated derivatives showed slight reduction of potency compared to the respective unsaturated derivatives. Compound containing a 16-membered ring as the P1-P2 ligand showed the most potent enzyme inhibitory and antiviral activity.

SUBMITTER: Ghosh AK 

PROVIDER: S-EPMC4133278 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature