New nitrogen containing substituents at the indole-2-carboxamide yield high potent and broad spectrum indolylarylsulfone HIV-1 non-nucleoside reverse transcriptase inhibitors.
New indolylarylsulfone (IAS) derivatives bearing nitrogen containing substituents at the indole-2-carboxamide inhibited the HIV-1 WT in MT-4 cells at low nanomolar concentrations. In particular, compound 9 was uniformly effective against the mutant Y181C, Y188L, and K103N HIV-1 strains; it was highly active against the multidrug resistant mutant IRLL98 HIV-1 strain bearing the K101Q, Y181C, and G190A mutations conferring resistance to NVP, DLV, and EFV and several HIV-1 clades A in PBMC.
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
Giuseppe
G
La Regina
Antonio
A
Coluccia
Andrea
A
Brancale
Francesco
F
Piscitelli
Valeria
V
Famiglini
Sandro
S
Cosconati
Giovanni
G
Maga
Alberta
A
Samuele
Emmanuel
E
Gonzalez
Bonaventura
B
Clotet
Dominique
D
Schols
José A
JA
Esté
Ettore
E
Novellino
Romano
R
Silvestri
D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D007211:Indoles / Q000737:chemistry*; D009154:Mutation; D009584:Nitrogen / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry* / Q000494:pharmacology*
D007211:Indoles; D018894:Reverse Transcriptase Inhibitors; D013450:Sulfones; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D009584:Nitrogen