460748-08-7Relevant articles and documents
Follow on-based optimization of the biphenyl-DAPYs as HIV-1 nonnucleoside reverse transcriptase inhibitors against the wild-type and mutant strains
Sang, Yali,Han, Sheng,Han, Shuwen,Pannecouque, Christophe,De Clercq, Erik,Zhuang, Chunlin,Chen, Fener
, (2019/05/21)
The present work follows our preliminary discovery of biphenyl diarylpyrimidines (DAPYs) as HIV-1 nonnucleoside reverse transcriptase inhibitors. Further structural optimization of biphenyl-DAPYs led to the identification of a new series of biphenyl-substituted thiophene[3,2-d]pyrimidine analogues by a scaffold-hopping strategy. Biological evaluation of this series showed that these compounds possessed up to single-digit nanomolar potency (EC50 = 7.8–526.2 nM) and prominently low toxicity (CC50 = 18.5–280.8 μM) against wild-type (WT) HIV-1-infected cells. Furthermore, the results also demonstrated that compounds 29–32 exhibited high, broad-spectrum antiviral effects against clinically observed HIV-1 mutants. Specifically, compound 30, which had the highest selectivity index (SI = 16094) and the best anti-reverse transcriptase ability (IC50 = 39 nM), displayed marked inhibitory activity (EC50 = 13.5, 9.4, 17.0, 52.0, and 58.2 nM) against WT, K103N, E138K, L100I, Y181C mutants and moderate activity against double mutants. This study provides important avenues for the further design of HIV-1 inhibitors.
Enthalpy-entropy compensation combined with cohesive free-energy densities for tuning the melting temperatures of cyanobiphenyl derivatives
Dutronc, Thibault,Terazzi, Emmanuel,Guenee, Laure,Buchwalder, Kerry-Lee,Spoerri, Aurore,Emery, Daniel,Mareda, Jiri,Floquet, Sebastien,Piguet, Claude
, p. 8447 - 8456 (2013/07/19)
This work illustrates how minor structural perturbations produced by methylation of 4′-(dodecyloxy)-4-cyanobiphenyl leads to enthalpy-entropy compensation for their melting processes, a trend which can be analyzed within the frame of a simple intermolecular cohesive model. The transformation of the melting thermodynamic parameters collected at variable temperatures into cohesive free-energy densities expressed at a common reference temperature results in a novel linear correlation, from which melting temperatures can be simply predicted from molecular volumes. In tune with temperature! The transformation of the melting thermodynamic parameters into cohesive free-energy densities (CFED) for 4′-(n-oxy)-i′-methyl-j-methyl-4-cyanobiphenyl (CnLi′,j) provides a novel linear correlation for predicting melting temperatures in a simple way. Copyright
Structure-activity relationships of arylbenzofuran H3 receptor antagonists
Gfesser, Gregory A.,Faghih, Ramin,Bennani, Youssef L.,Curtis, Michael P.,Esbenshade, Timothy A.,Hancock, Arthur A.,Cowart, Marlon D.
, p. 2559 - 2563 (2007/10/03)
An SAR study of histamine H3 receptor antagonists based on substituted (R)-2-methyl-1-[2-(5-phenyl-benzofuran-2-yl)-ethyl]-pyrrolidines is presented.
