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.
Rocheblave
Luc
L
Laboratoire de Chimie Biomoléculaire, Faculté des Sciences de Luminy, case 901, Université de la Méditerranée, 70 route Léon Lachamp, 13288 Marseille Cedex 9, France.
Bihel
Frédéric
F
De Michelis
Céline
C
Priem
Ghislaine
G
Courcambeck
Jérôme
J
Bonnet
Brice
B
Chermann
Jean-Claude
JC
Kraus
Jean-Louis
JL
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