35623-11-1Relevant academic research and scientific papers
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.
PYRIDINE COMPOUND SUBSTITUTED WITH AZOLE
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Paragraph 0943, (2020/07/07)
The present invention provides a compound represented by formula [I] shown below or a pharmaceutically acceptable salt thereof that has an inhibitory effect on 20-HETE producing enzyme. (in formula [I] above, the structure represented by formula [II] below: represents any of the structures represented by formula group [III] below: R1, R2, R3, and R4 independently represent a hydrogen atom, a fluorine atom, methyl, or the like, R5 represents any of the structures represented by formula group [IV]:
BACE-2 INHIBITORY COMPOUNDS AND RELATED METHODS OF USE
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Paragraph 0140; 0144; 0157; 0158, (2017/05/02)
Provided herein are novel compounds of Formulae I-III, and methods of using the same to selectively inhibit BACE2.
COMPOUNDS, IN PARTICULAR FOR USE IN THE TREATMENT OF A DISEASE OR CONDITION FOR WHICH A BROMODOMAIN INHIBITOR IS INDICATED
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Page/Page column 50, (2016/01/25)
The invention relates to a compound for use in the treatment of a disease or condition for which a bromodomain inhibitor is indicated characterized by a general formula (1) and a compound according to formula (3).
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.
N'-Alkylaminosulfonyl Analogues of 6-Fluorobenzylideneindolinones with Desirable Physicochemical Profiles and Potent Growth Inhibitory Activities on Hepatocellular Carcinoma
Chen, Xiao,Yang, Tianming,Deivasigamani, Amudha,Shanmugam, Muthu K.,Hui, Kam-Man,Sethi, Gautam,Go, Mei-Lin
supporting information, p. 1548 - 1558 (2015/09/07)
The benzylideneindolinone 6-chloro-3-(3′-trifluoromethylbenzylidene)-1,3-dihydroindol-2-one (4) was reported to exhibit potent and selective growth inhibitory effects on hepatocellular carcinoma (HCC). Corroborative evidence supported multi-receptor tyrosine kinase (RTK) inhibition as a possible mode of action. However, the poor physicochemical properties of 4 limited its furtherance as a lead compound. In this study, the modification of 4 was investigated with the aim of improving its potency and physicochemical profile. The 6-fluorobenzylideneindolinone 3-12 bearing a 3′-N-propylaminosulfonyl substituent was found to be a promising substitute. Compound 3-12 [6-fluoro-3-(3′-N-propylaminosulfonylbenzylidene)-1,3-dihydroindol-2-one] was found to be tenfold more soluble than 4 and to have sub-micromolar growth inhibitory activities on HCC cells. It is apoptogenic and inhibits the phosphorylation of several RTKs in HuH7, of which the inhibition of FGFR4 and HER3 are prominent. Compound 3-12 decreased the tumor load in a physiologically relevant orthotopic HCC xenograft murine model. Structure-activity relationships support pivotal roles for the fluoro and N′-propylaminosulfonyl moieties in enhancing cell-based activity and moderating the physicochemical profile (solubility, permeability) of 3-12.
BENZYLIDENE-INDOLINONE COMPOUNDS AND THEIR MEDICAL USE
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Paragraph 0233; 0236-0237, (2013/03/26)
Compounds of general formula I: wherein R1a, R1b, R2, R3a, R3b and X are as defined herein are tyrosine kinase inhibitors and are useful for the treatment of various diseases and conditions, for examp
NOVEL QUINOLINE ESTERS USEFUL FOR TREATING SKIN DISORDERS
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Page/Page column 16, (2012/01/15)
Disclosed are quinoline esters of Formula (I): which are useful as Liver X receptors (LXR) modulators. Pharmaceutical compositions containing quinoline esters of Formula (I) and the use of quinoline esters of Formula (I) in the safe treatment of various s
NOVEL 1,2,4 OXADIAZOLE COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 63, (2009/12/28)
The invention relates to 1,2,4 oxadiazole compounds and analogs thereof, represented by formula (II), and compositions and methods of use thereof.
PHARMACEUTICAL COMPOSITIONS AND THEIR METHODS OF USE
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Page/Page column 56, (2008/12/06)
The invention relates to a composition comprising a neuronal nicotinic receptor ligand and an α4β2 positive allosteric modulator, a method of using the same, and a related article of manufacture.
