Novel lopinavir analogues incorporating heterocyclic replacements of six-member cyclic urea--synthesis and structure-activity relationships

Hing L Sham; David A Betebenner; William Rosenbrook; Thomas Herrin; Ayda Saldivar; Sudthida Vasavanonda; Jacob J Plattner; Daniel W Norbeck

doi:10.1016/j.bmcl.2004.02.089

Novel lopinavir analogues incorporating heterocyclic replacements of six-member cyclic urea--synthesis and structure-activity relationships

Bioorg Med Chem Lett. 2004 May 17;14(10):2643-5. doi: 10.1016/j.bmcl.2004.02.089.

Authors

Hing L Sham¹, David A Betebenner, William Rosenbrook, Thomas Herrin, Ayda Saldivar, Sudthida Vasavanonda, Jacob J Plattner, Daniel W Norbeck

Affiliation

¹ Pharmaceutical Discovery, R4MA Building AP-10, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. [email protected]

PMID: 15109669
DOI: 10.1016/j.bmcl.2004.02.089

Abstract

The HIV protease inhibitor ABT-378 (lopinavir) has a six-member cyclic urea in the P-2 position. A series of analogues in which the six-member cyclic urea is replaced by various heterocycles was synthesized and the structure-activity relationships explored.

MeSH terms

Cell Line, Tumor
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / pharmacology
HIV-1 / drug effects
Heterocyclic Compounds / chemistry
Humans
Lopinavir
Microbial Sensitivity Tests
Pyrimidinones / chemical synthesis
Pyrimidinones / pharmacology*
Structure-Activity Relationship
Urea / chemistry

Substances

Enzyme Inhibitors
HIV Protease Inhibitors
Heterocyclic Compounds
Pyrimidinones
Lopinavir
Urea