Synthesis and antiviral activities of the major metabolites of the HIV protease inhibitor ABT-378 (Lopinavir)

H L Sham; D A Betebenner; T Herrin; G Kumar; A Saldivar; S Vasavanonda; A Molla; D J Kempf; J J Plattner; D W Norbeck

doi:10.1016/s0960-894x(01)00243-8

Synthesis and antiviral activities of the major metabolites of the HIV protease inhibitor ABT-378 (Lopinavir)

Bioorg Med Chem Lett. 2001 Jun 4;11(11):1351-3. doi: 10.1016/s0960-894x(01)00243-8.

Authors

H L Sham¹, D A Betebenner, T Herrin, G Kumar, A Saldivar, S Vasavanonda, A Molla, D J Kempf, J J Plattner, D W Norbeck

Affiliation

¹ Pharmaceutical Discovery, D47B, Building AP-10, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. hing.l.sham@abbott.com

PMID: 11378352
DOI: 10.1016/s0960-894x(01)00243-8

Abstract

The HIV protease inhibitor ABT-378 (Lopinavir) is metabolized rapidly and extensively by CYP-3A4 catalyzed oxidation. Three of the major metabolites identified were synthesized and their antiviral (HIV) activities determined.

MeSH terms

Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / chemistry
Anti-HIV Agents / metabolism
Anti-HIV Agents / pharmacology
Cells, Cultured
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System / metabolism*
HIV / drug effects
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / chemistry
HIV Protease Inhibitors / metabolism
HIV Protease Inhibitors / pharmacology
Humans
Lopinavir
Microbial Sensitivity Tests
Mixed Function Oxygenases / metabolism*
Pyrimidinones / chemical synthesis
Pyrimidinones / chemistry
Pyrimidinones / metabolism*
Pyrimidinones / pharmacology

Substances

Anti-HIV Agents
HIV Protease Inhibitors
Pyrimidinones
Lopinavir
Cytochrome P-450 Enzyme System
Mixed Function Oxygenases
CYP3A protein, human
Cytochrome P-450 CYP3A