41263-74-5Relevant articles and documents
Molecular modeling studies, synthesis and biological evaluation of dabigatran analogues as thrombin inhibitors
Dong, Ming-Hui,Chen, Hai-Feng,Ren, Yu-Jie,Shao, Fang-Ming
, p. 73 - 84 (2016)
In this work, 48 thrombin inhibitors based on the structural scaffold of dabigatran were analyzed using a combination of molecular modeling techniques. We generated three-dimensional quantitative structure-activity relationship (3D-QSAR) models based on three alignments for both comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) to highlight the structural requirements for thrombin protein inhibition. In addition to the 3D-QSAR study, Topomer CoMFA model also was established with a higher leave-one-out cross-validation q2 and a non-cross-validation r2, which suggest that the three models have good predictive ability. The results indicated that the steric, hydrophobic and electrostatic fields play key roles in QSAR model. Furthermore, we employed molecular docking and re-docking simulation explored the binding relationship of the ligand and the receptor protein in detail. Molecular docking simulations identified several key interactions that were also indicated through 3D-QSAR analysis. On the basis of the obtained results, two compounds were designed and predicted by three models, the biological evaluation in vitro (IC50) demonstrated that these molecular models were effective for the development of novel potent thrombin inhibitors.
A chemical approach for the synthesis of the DNA-binding domain of the oncoprotein MYC
Calo-Lapido, Renata,Penas, Cristina,Jiménez-Balsa, Adrián,Vázquez, M. Eugenio,Mascare?as, José L.
, p. 6748 - 6752 (2019)
We describe the first chemical synthesis of a functional mutant of the DNA binding domain of the oncoprotein MYC, using two alternative strategies which involve either one or two Native Chemical Ligations (NCLs). Both routes allowed the efficient synthesis of a miniprotein which is capable of heterodimerizing with MAX, and replicate the DNA binding of the native protein. The versatility of the reported synthetic approach enabled the straightforward preparation of MYC and Omomyc analogues, as well as fluorescently labeled derivatives.
Design, synthesis and biological activity evaluation of novel methyl substituted benzimidazole derivatives
Liu, Qianqian,Ren, Yujie,Zhang, Tianrong
, (2020/03/03)
Ten new dabigatran derivatives (7a–j) with high docking scoring were designed, synthesised and biologically evaluated. The inhibitory in vitro activity of these compounds on thrombin was evaluated on the basis of preliminary activity screening results. The IC50 values of compounds 7a, 7d and 7j were 1.92, 2.17 and 1.54 nM, respectively, and are equivalent to the dabigatran (IC50 = 1.20 nM). Therefore, the most active compound, 7j, was selected to further investigate the anticoagulant activity in rats. Compound 7j presented excellent in vivo inhibitory effects on arteriovenous thrombosis, and the inhibition rate was (84.19 ± 1.14) %. The anticoagulant activity of compound 7k synthesised in the previous work was evaluated in vivo, and its inhibition rate was (85.58 ± 2.89) %. This rate was nearly equivalent to that of dabigatran (85.07 ± 0.61) %. Results indicated that compounds 7a, 7d, 7j and 7k can be further studied as novel antithrombin drug candidates.
“On Water” promoted N-arylation reactions using Cu (0)/myo-inositol catalytic system
Zhou, Qifan,Du, Fangyu,Chen, Yuanguang,Fu, Yang,Chen, Guoliang
supporting information, p. 1938 - 1941 (2019/06/24)
Myo-inositol is originally applied as a cardiovascular medicine in clinic, which can be multi-ton manufactured via extraction from the byproducts in agricultural product processing such as defatted rice bran and corn-soaking water. Herein, the application of myo-inositol (MI) as a novel versatile tridentate O-donor ligand has been first described for promoting Cu-catalyzed amination reaction in aqueous medium.