122399-90-0Relevant academic research and scientific papers
Design, synthesis, and bioevaluation of a novel class of (E)-4-oxo-crotonamide derivatives as potent antituberculosis agents
Ren, Jinfeng,Xu, Jian,Zhang, Guoning,Xu, Changliang,Zhao, LiLi,You, XueFu,Wang, Yucheng,Lu, Yu,Yu, Liyan,Wang, Juxian
, p. 539 - 543 (2019/01/09)
A series of novel (E)-4-oxo-2-crotonamide derivatives were designed and synthesized to find potent antituberculosis agents. All the target compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv(MTB). Results reveal that 4-phenyl moiety at part A and short methyl group at part C were found to be favorable. Most of the derivatives displayed promising activity against MTB with MIC ranging from 0.125 to 4 μg/mL. Especially, compound IIIa16 was found to have the best activity with MIC of 0.125 μg/mL against MTB and with MIC in the range of 0.05–0.48 μg/mL against drug-resistant clinical MTB isolates.
Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-γ-Hydroxycrotonic Acid (T-HCA) Analogs
Krall, Jacob,Jensen, Claus Hatt,Bavo, Francesco,Falk-Petersen, Christina Birkedahl,Haugaard, Anne St?hr,Vogensen, Stine Byskov,Tian, Yongsong,Nittegaard-Nielsen, Mia,Sigurdardóttir, Sara Bj?rk,Kehler, Jan,Kongstad, Kenneth Thermann,Gloriam, David E.,Clausen, Rasmus Pr?torius,Harps?e, Kasper,Wellendorph, Petrine,Fr?lund, Bente
, p. 9022 - 9039 (2017/11/14)
γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A molecular hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar Ki) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified molecular features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.
