A refined pharmacophore model for HIV-1 integrase inhibitors: Optimization of potency in the 1H-benzylindole series.
We report herein the development of a new three-dimensional pharmacophore model for HIV-1 integrase inhibitors which led to the discovery of some 4-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acids that are able to specifically inhibit the strand transfer step of integration at nanomolar concentration. The synthesis of the new designed molecules is also described.
De Luca
Laura
L
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy.
Barreca
Maria Letizia
ML
Ferro
Stefania
S
Iraci
Nunzio
N
Michiels
Martine
M
Christ
Frauke
F
Debyser
Zeger
Z
Witvrouw
Myriam
M
Chimirri
Alba
A
D002087:Butyrates / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D024882:Drug Resistance, Viral; D019427:HIV Integrase / Q000187:drug effects* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008956:Models, Chemical; D013329:Structure-Activity Relationship
D002087:Butyrates; D019428:HIV Integrase Inhibitors; D007211:Indoles; D019427:HIV Integrase