Synthesis of potent C(2)-symmetric, diol-based hiv-1 protease inhibitors. Investigation of thioalkyl and thioaryl P1/P1' substituents.
The synthesis of novel, potent diol-based HIV-1 protease inhibitors, having either -SAr, -SCH(2)Ar, or -SCH(2)R groups as P1/P1' substituents is described. They can be prepared using a straightforward synthesis involving a thiol nucleophilic ring opening of a diepoxide. Inhibitor 13 was found to be a potent inhibitor of HIV-1 PR, showing good antiviral activity in a cell-based assay.
Mühlman
A
A
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
Classon
B
B
Hallberg
A
A
Samuelsson
B
B
D002460:Cell Line; D003001:Cloning, Molecular; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D017320:HIV Protease Inhibitors; C438590:N1,N6-di-(hydroxy-1-indanyl)-3,4-dihydroxy-2,5-di-(thiophen-3-ylsulfanyl)hexanediamide; D013876:Thiophenes; D016333:HIV Protease