866941-30-2Relevant academic research and scientific papers
A refined pharmacophore model for HIV-1 integrase inhibitors: Optimization of potency in the 1H-benzylindole series
De Luca, Laura,Barreca, Maria Letizia,Ferro, Stefania,Iraci, Nunzio,Michiels, Martine,Christ, Frauke,Debyser, Zeger,Witvrouw, Myriam,Chimirri, Alba
, p. 2891 - 2895 (2008/12/21)
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.
New 4-[(1-benzyl-1H-indol-3-yl)carbonyl]-3-hydroxyfuran-2(5H)-ones, β-diketo acid analogs as HIV-1 integrase inhibitors
Ferro, Stefania,Barreca, Maria Letizia,De Luca, Laura,Rao, Angela,Monforte, Anna Maria,Debyser, Zeger,Witvrouw, Myriam,Chimirri, Alba
, p. 292 - 298 (2008/02/10)
In addition to our recent report on a series of rationally designed benzylindolyldiketo acids acting as potent HIV-1 integrase strand transfer inhibitors, we disclose the results obtained with novel compounds chemically modified on the diketo acid moiety in order to investigate its influence on the biological activity and cytotoxicity. The activity of designed and synthesized 4-[(1-benzyl-1H-indol-3-yl)carbonyl]-3-hydroxyfuran-2(5H)-one derivatives lies in the micromolar range with regard to HIV IN enzymatic activity. The microwave-assisted synthesis was employed in some steps of the chemical procedures.
Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors
Barreca, Maria Letizia,Ferro, Stefania,Rao, Angela,De Luca, Laura,Zappalà, Maria,Monforte, Anna-Maria,Debyser, Zeger,Witvrouw, Myriam,Chimirri, Alba
, p. 7084 - 7088 (2007/10/03)
Using a training set of diketo-like acid HIV-1 integrase (IN) strand-transfer inhibitors, a 3D pharmacophore model was derived having quantitative predictive ability in terms of activity. The best statistical hypothesis consisted of four features (one hydrophobic aromatic region, two hydrogen-bond acceptors, and one hydrogen-bond donor) with r of 0.96. The resulting pharmacophore model guided the rational design of benzylindoles as new potent IN inhibitors, whose microwave-assisted synthesis and biological evaluation are reported.
