N-aminoimidazole derivatives inhibiting retroviral replication via a yet unidentified mode of action.
The synthesis of a series of N-aminoimidazoles (NAIMs) with an uncommon spectrum of antiretroviral activity is described. From a group of 60 closely related molecules, we were able to subdivide the molecules in different groups based on their anti-HIV and anti-SIV activity in vitro: (i) molecules acting on a new, immediate postintegration step, (ii) molecules acting on both postintegration and HIV-1 reverse transcriptase (RT) as NNRTI, and (iii) molecules that mainly act at the HIV-1 RT according to an NNRTI-type mode of action.
Lagoja
Irene M
IM
Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, Belgium.
Pannecouque
Christophe
C
Van Aerschot
Arthur
A
Witvrouw
Myriam
M
Debyser
Zeger
Z
Balzarini
Jan
J
Herdewijn
Piet
P
De Clercq
Erik
E
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007093:Imidazoles; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase