Synthesis of a New Lopinavir Phosphinic Analog as HIV-1 Inhibitor

Abstract

HIV/AIDS has been one of the most devastating global diseases. HIV-1 protease proteolytic action is responsible for the manufacture of grown, infectious species, consequently HIV-1 protease has become an attractive goal in the treatment and therapy of HIV. Several HIV-1 protease inhibitors based therapeutic agents are under investigation or currently in the market. Lopinavir (ABT-378) has a great value in this research field. Therefore, different methods have appeared aiming to develop efficient analogs by the utilization of variable techniques, since Lopinavir had showed low bioavailability when being prescribed alone, and various side effects after the combination of Lopinavir with another HIV-1 inhibitors such as Ritonavir, which is available in the markets nowadays under the brand name Kaletra. Replacement of the hydroxyethylene moiety in Lopinavir structure, which is responsible for the monohydroxylated metabolites with the stable to hydrolysis phosphinic group has been considered, since that hydroxyl group in the central core is responsible for the interaction with the carboxylic acid in the catalytic aspartyl residue of HIV-1 by hydrogen bonding and consequently supports the drug affinity to the protease. The small scale processes for the synthetic strategies for the new candidate phosphinic analog of Lopinavir protease inhibitor (PL1) is presented here in along with some preliminary pharmacological data.