138240-34-3Relevant academic research and scientific papers
Discovery of 3,6-disubstutited-imidazo[1,2-a]pyridine derivatives as a new class of CLK1 inhibitors
Zhang, Yun,Xia, Anjie,Zhang, Shiyu,Lin, Guifeng,Liu, Jingming,Chen, Pei,Mu, Bo,Jiao, Yan,Xu, Wenwen,Chen, Mingxin,Li, Linli
, (2021)
Inhibition of cdc2-like kinase1 (CLK1) could efficiently induce autophagy and it has been thought as a potential target for treatment of autophagy-related diseases. Herein we report the discovery of a series of 3,6-disubstutited-imidazo[1,2-a]pyridine derivatives as a new class of CLK1 inhibitors. Among them, compound 9e is the most potent one, which exhibits an IC50 value of 4 nM against CLK1 kinase. In vitro, this compound reduces the phosphorylation level of the typical downstream substrates of CLK1 and affects their subcellular redistribution. Further study indicates that 9e is efficient to induce autophagy. Overall, this study provides a promising lead compound for drug discovery targeting CLK1 kinase.
Synthesis of 2-guanidinyl pyridines and their trypsin inhibition and docking
Ahmed Al-Hadhrami, Nahlah,Evans, Paul,Ladwig, Angelique,Paul G. Malthouse, J.,Rahman, Adeyemi,Rozas, Isabel
, (2020)
A range of guanidine-based pyridines, and related compounds, have been prepared (19 examples). These compounds were evaluated in relation to their competitive inhibition of bovine pancreatic trypsin. Results demonstrate that compounds in which the guanidinyl substituent can form an intramolecular hydrogen bond (IMHB) with the pyridinyl nitrogen atom (6a–p) are better trypsin inhibitors than their counterparts (10–13) that are unable to form an IMHB. Among the compounds 6a–p, examples containing a 5-halo substituent were, generally, found to be better trypsin inhibitors. This trend was inversely related to electronegativity, thus, 1-(5-iodopyridin-2-yl)guanidinium ion 6e (Ki = 0.0151 mM) was the optimum inhibitor in the 5-halo series. Amongst the isomeric methyl substituted compounds, 1-(3-methylpyridin-2-yl)guanidinium ion 6h demonstrated optimum levels of trypsin inhibition (Ki = 0.0140 mM). In order to rationalise the measured enzyme inhibition, selected compounds were docked with bovine and human trypsin with a view to understanding active site occupancy and taken together with the Ki values the order of inhibitory ability suggests that the 5-halo 2-guanidinyl pyridine inhibitors form a halogen bond with the catalytically active serine hydroxy group.
Preparation and application of imidazo aromatic ring compounds
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Paragraph 0151-0156, (2020/05/02)
The invention provides preparation and application of imidazo aromatic ring compounds, and particularly provides compounds as shown in the following formula I. The definition of each group is as shownin the specification. The compounds have TRK kinase inh
Convenient two-step one-pot synthesis of 3-substituted imidazo[1,2-a]pyridines and imidazo[1,2-b]pyridazines
Fan, Hongli,Li, Fenghai
, (2018/05/23)
Abstract: A convenient and novel two-step one-pot method for the synthesis of 3-substituted imidazo[1,2-a]pyridines and 3-substituted imidazo[1,2-b]pyridazines was developed through the reaction of heterocyclic amines and N,?N-dimethylformamide dimethyl a
Design and synthesis of imidazopyridine analogues as inhibitors of phosphoinositide 3-kinase signaling and angiogenesis
Kim, Okseon,Jeong, Yujeong,Lee, Hyunseung,Hong, Sun-Sun,Hong, Sungwoo
experimental part, p. 2455 - 2466 (2011/06/20)
Phosphatidylinositol 3-kinase α (PI3Kα) is an important regulator of intracellular signaling pathways, controlling remarkably diverse arrays of physiological processes. Because the PI3K pathway is frequently up-regulated in human cancers, the inhibition of PI3Kα can be a promising approach to cancer therapy. In this study, we have designed and synthesized a new series of imidazo[1,2-a]pyridine derivatives as PI3Kα inhibitors through the fragment-growing strategy. By varying groups at the 3- and 6-positions of imidazo[1,2-a]pyridines, we studied the structure-activity relationships (SAR) profiles and identified a series of potent PI3Kα inhibitors. Representative derivatives showed good activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.
THIOZOLIDINEDIONE DERIVATIVES AS P13 KINASE INHIBITORS
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Page/Page column 49-50, (2008/06/13)
Invented is a method of inhibiting the activity/function of PB kinases using thiozolidinedione derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of thiozolidinedione derivatives.
Chemistry of Amidines. Part 1. Determination of the Site of Initial Protonation in N'-Pyridylformamidines
Cunningham, Ian D.,Blanden, James S.,Llor, Juan,Munoz, Luis,Sharratt, Andrew P.
, p. 1747 - 1750 (2007/10/02)
A series of substituted N,N-dimethyl-N'-pyridylformamidines has been synthesised and the pKa values of the conjugate acids have been measured in water at 25 deg C.Consideration of the pKa values shows that initial protonation is predominantly on the imino nitrogen of the amidine system rather than on the pyridyl nitrogen.The effect of the protonation on the 1H and 13C NMR spectra of the amidines is discussed.
