Synthesis and antiviral activity of new anti-HIV amprenavir bioisosteres.
Starting from the chemical structure of the recent FDA-approved anti-HIV drug Amprenavir (Agenerase), a potent HIV-protease inhibitor, we have designed new series of Amprenavir bioisoteres in which the methylene group of the benzyl group was replaced by a sulfur atom. This structural modification has required an original multistep synthesis. Unfortunately, introduction of the sulfur atom abolished or drastically decreased both inhibitory activity on recombinant HIV protease and HIV infection protection on MT4 cell cultures.
Laboratoire de Chimie Biomoléculaire, Faculté des Sciences de Luminy, case 901, Université de la Méditerranée, 70 route Léon Lachamp, 13288 Marseille Cedex 9, France.
Luc
L
Rocheblave
Frédéric
F
Bihel
Céline
C
De Michelis
Ghislaine
G
Priem
Jérôme
J
Courcambeck
Brice
B
Bonnet
Jean-Claude
JC
Chermann
Jean-Louis
JL
Kraus
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates; D002460:Cell Line; D005663:Furans; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D014779:Virus Replication
D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D016333:HIV Protease