title: A refined pharmacophore model for HIV-1 integrase inhibitors: Optimization of potency in the 1H-benzylindole series.
abstract: 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.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Barreca
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferro
authors.forename: Nunzio
authors.initials: N
authors.lastname: Iraci
authors.forename: Martine
authors.initials: M
authors.lastname: Michiels
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: 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
chemical_list: D002087:Butyrates; D019428:HIV Integrase Inhibitors; D007211:Indoles; D019427:HIV Integrase