Novel 1,3-dihydro-benzimidazol-2-ones and their analogues as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
A series of novel benzimidazolones and their analogues, characterized by the presence of one or more methyl groups or other bioisosteric moieties at different positions of the phenyl ring at N-1, were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Most of the new compounds proved to be highly effective in inhibiting both HIV-1 replication in MT4 cells with minimal cytotoxicity and RT enzyme at nanomolar concentrations. Some derivatives were also tested against RTs containing single amino acid mutations responsible for resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). The different potencies displayed by the new compounds were studied using molecular modeling.
Monforte
Anna-Maria
AM
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. ammonforte@pharma.unime.it
Logoteta
Patrizia
P
De Luca
Laura
L
Iraci
Nunzio
N
Ferro
Stefania
S
Maga
Giovanni
G
De Clercq
Erik
E
Pannecouque
Christophe
C
Chimirri
Alba
A
D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D001562:Benzimidazoles; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase