4-hydroxy-5,6-dihydro-2H-pyran-2-ones.3. Bicyclic and hetero-aromatic ring systems as 3-position scaffolds to bind to S1' and S2' of the HIV-1 protease enzyme

E L Ellsworth; J Domagala; J V Prasad; S Hagen; D Ferguson; T Holler; D Hupe; N Graham; C Nouhan; P J Tummino; G Zeikus; E A Lunney

doi:10.1016/s0960-894x(99)00332-7

4-hydroxy-5,6-dihydro-2H-pyran-2-ones.3. Bicyclic and hetero-aromatic ring systems as 3-position scaffolds to bind to S1' and S2' of the HIV-1 protease enzyme

Bioorg Med Chem Lett. 1999 Jul 19;9(14):2019-24. doi: 10.1016/s0960-894x(99)00332-7.

Authors

E L Ellsworth¹, J Domagala, J V Prasad, S Hagen, D Ferguson, T Holler, D Hupe, N Graham, C Nouhan, P J Tummino, G Zeikus, E A Lunney

Affiliation

¹ Department of Chemistry, Parke-Davis Pharmaceutical Research Division of the Warner-Lambert Company, Ann Arbor, MI 48105, USA.

PMID: 10450973
DOI: 10.1016/s0960-894x(99)00332-7

Abstract

5,6-Dihydro-2H-pyran-2-ones are potent inhibitors of HIV-1 protease, which bind to the S1, S2, S1', and S2' pockets and have a unique binding mode with the catalytic aspartyl groups and the flap region of the enzyme. Efforts to explore 3-position heterocyclic scaffolds that bind to the S1' and S2' pockets have provided a number of selected analogs that display high HIV-1 protease inhibitory activity. reserved.

MeSH terms

Binding Sites
Computer Simulation
Drug Design
HIV Protease / chemistry
HIV Protease / metabolism*
HIV Protease Inhibitors / chemistry*
HIV Protease Inhibitors / metabolism*
HIV Protease Inhibitors / pharmacology
Hydrocarbons, Aromatic / chemistry
Hydrogen-Ion Concentration
Inhibitory Concentration 50
Models, Molecular
Molecular Structure
Pyrones / chemical synthesis*
Pyrones / metabolism
Pyrones / pharmacology*
Software
Structure-Activity Relationship
Sugar Alcohols / metabolism
Valine / analogs & derivatives
Valine / metabolism

Substances

HIV Protease Inhibitors
Hydrocarbons, Aromatic
Pyrones
Sugar Alcohols
A 74704
HIV Protease
Valine