1576-45-0Relevant articles and documents
Design and synthesis of newer N-benzimidazol-2yl benzamide analogues as allosteric activators of human glucokinase
Singh, Sukhbir,Arora, Sandeep,Dhalio, Ervon,Sharma, Neelam,Arora, Kunal,Grewal, Ajmer Singh
, p. 760 - 770 (2021/01/20)
Allosteric activators of human glucokinase (GK) had revealed significant hypoglycemic effects for therapy of type-2 diabetes (T2D) in animal as well as human models. Some newer N-benzimidazol-2yl substituted benzamide analogues were prepared and assessed for activation of GK accompanied by molecular docking investigations for predicting the bonding interactions of these derivatives with the residues in allosteric site of GK protein. Amongst the derivatives synthesized, compounds 2 and 7 strongly increased catalytic action of GK (GK activation fold >2.0 in comparison to control) in vitro. The results of in-vitro testing were supported by the molecular docking investigations of these analogues with GK protein’s allosteric site residues (showed appreciable H-bond interactions with Arg63 residue of GK). Derivatives investigated in present study afforded few lead compounds for the discovery of harmless and strong allosteric GK activating compounds for treating T2D.
Synthesis method of belinostat
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, (2016/11/14)
The invention discloses a synthesis method of belinostat. The method comprises the following steps: by using benzoic acid as an initial material, performing six reaction steps of chlorosulfonation, aniline condensation, reduction, oxidation, Witting-Horner condensation and hydrolysis, acylating chlorination and hydroxylamine condensation to prepare a target compound. The initial material benzoic acid of the method is cheap and easy to obtain, the sulfonylation and acylating chlorination reaction are realized through one step, the preparation time is shortened, and the yield is improved. In the oxidation process, an oxidizing reagent which is cheap and does not contains metal ion is adopted so that the active ingredients easily achieve the requirement of heavy metal ion limitation, and the pollution to the environment is reduced. All reaction intermediates of the method are solid and can be purified through a salt formation or recrystallization method, the time-consuming and labor-consuming column chromatography purification is avoided, and the method is suitable for industrial production.
Synthesis and biological evaluation of novel (E)-N′-(2,3-dihydro-1H-inden-1-ylidene) benzohydrazides as potent LSD1 inhibitors
Zhou, Yang,Li, Yan,Wang, Wen-Jing,Xiang, Pu,Luo, Xin-Mei,Yang, Li,Yang, Sheng-Yong,Zhao, Ying-Lan
, p. 4552 - 4557 (2016/08/24)
Lysine specific demethylase 1 (LSD1) plays an important role in regulating histone lysine methylation at residues K4 and K9 on histone H3 and is recognized as an attractive therapeutic target in multiple malignancies. In this study, a series of novel (E)-N′-(2,3-dihydro-1H-inden-1-ylidene) benzohydrazides were synthesized and biologically evaluated for their potential LSD1 inhibitory effect. Among them, compounds 5a and 5n showed the most potent LSD1 inhibitory activity with IC50values of 1.4 and 1.7?nM, respectively, which were about 10 times more potent compared with (E)-N-(1-(5-chloro-2-hydroxyphenyl) ethylidene)-3-(morpholinosulf-only) benzohydrazide (J. Med. Chem. 2013, 56, 9496–9508; as reference compound). Compounds 5a and 5n also exhibited marked anti-proliferation activities against cancer cell lines that highly expressed LSD1. These results suggest that these optimized compounds might be served as promising LSD1 inhibitors against cancer, which merit further study.
