title: 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.
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.
authors.affiliation: Department of Chemistry, Parke-Davis Pharmaceutical Research Division of the Warner-Lambert Company, Ann Arbor, MI 48105, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Ellsworth
authors.forename: J
authors.initials: J
authors.lastname: Domagala
authors.forename: J V
authors.initials: JV
authors.lastname: Prasad
authors.forename: S
authors.initials: S
authors.lastname: Hagen
authors.forename: D
authors.initials: D
authors.lastname: Ferguson
authors.forename: T
authors.initials: T
authors.lastname: Holler
authors.forename: D
authors.initials: D
authors.lastname: Hupe
authors.forename: N
authors.initials: N
authors.lastname: Graham
authors.forename: C
authors.initials: C
authors.lastname: Nouhan
authors.forename: P J
authors.initials: PJ
authors.lastname: Tummino
authors.forename: G
authors.initials: G
authors.lastname: Zeikus
authors.forename: E A
authors.initials: EA
authors.lastname: Lunney
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D012984:Software; D013329:Structure-Activity Relationship; D013402:Sugar Alcohols / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D017320:HIV Protease Inhibitors; D006841:Hydrocarbons, Aromatic; D011753:Pyrones; D013402:Sugar Alcohols; C065300:A 74704; D016333:HIV Protease; D014633:Valine