Discovery of novel benzimidazolones as potent non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains.
Molecular modeling studies led to the rational discovery of N(1)-arylsulfonyl-1,3-dihydro-2H-benzimidazol-2-one as a novel template for the design of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are active against wild-type and mutant strains of HIV-1. It is worth noting that compound 3 proved to have antiretroviral activity similar to that of efavirenz and greater than that of nevirapine, two of the three NNRTIs currently available in antiretroviral therapy.
Barreca
Maria Letizia
ML
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. barreca@pharma.unime.it
Rao
Angela
A
De Luca
Laura
L
Iraci
Nunzio
N
Monforte
Anna-Maria
AM
Maga
Giovanni
G
De Clercq
Erik
E
Pannecouque
Christophe
C
Balzarini
Jan
J
Chimirri
Alba
A
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D048588:Benzoxazines / Q000494:pharmacology; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003521:Cyclopropanes; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz