Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-resistant viral strains

Yuan Cheng; Fengqi Zhang; Thomas A Rano; Zhijian Lu; William A Schleif; Lori Gabryelski; David B Olsen; Mark Stahlhut; Carrie A Rutkowski; Jiunn H Lin; Lixia Jin; Emilio A Emini; Kevin T Chapman; James R Tata

doi:10.1016/s0960-894x(02)00424-9

Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-resistant viral strains

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2419-22. doi: 10.1016/s0960-894x(02)00424-9.

Authors

Yuan Cheng¹, Fengqi Zhang, Thomas A Rano, Zhijian Lu, William A Schleif, Lori Gabryelski, David B Olsen, Mark Stahlhut, Carrie A Rutkowski, Jiunn H Lin, Lixia Jin, Emilio A Emini, Kevin T Chapman, James R Tata

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. yuan_cheng@merck.com

PMID: 12161147
DOI: 10.1016/s0960-894x(02)00424-9

Abstract

Indinavir analogues with blocked metabolism sites show highly improved pharmacokinetic profiles in animals. The cis-aminochromanol substituted analogues exhibited excellent potency against both the wild-type (NL4-3) virus and protease inhibitor-resistant HIV strains.

MeSH terms

Animals
Area Under Curve
Dogs
Drug Resistance
HIV / drug effects*
HIV Protease / drug effects
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / metabolism
HIV Protease Inhibitors / pharmacokinetics
Humans
Indinavir / analogs & derivatives*
Indinavir / metabolism
Indinavir / pharmacokinetics
Inhibitory Concentration 50
Metabolic Clearance Rate
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

HIV Protease Inhibitors
Indinavir
HIV Protease