19005-63-1Relevant articles and documents
Discovery of N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin- 2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline (EW-7197): A highly potent, selective, and orally bioavailable inhibitor of TGF-β type I receptor kinase as cancer immunotherapeutic/antifibrotic agent
Jin, Cheng Hua,Krishnaiah, Maddeboina,Sreenu, Domalapally,Subrahmanyam, Vura B.,Rao, Kota S.,Lee, Hwa Jeong,Park, So-Jung,Park, Hyun-Ju,Lee, Kiho,Sheen, Yhun Yhong,Kim, Dae-Kee
supporting information, p. 4213 - 4238 (2014/06/09)
A series of 2-substituted-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6- methylpyridin-2-yl)imidazoles was synthesized and evaluated to optimize a prototype inhibitor of TGF-β type I receptor kinase (ALK5), 6. Combination of replacement of a quinoxalin-6-yl moiety of 6 with a [1,2,4]triazolo[1,5-a] pyridin-6-yl moiety, insertion of a methyleneamino linker, and a o-F substituent in the phenyl ring markedly increased ALK5 inhibitory activity, kinase selectivity, and oral bioavailability. The 12b (EW-7197) inhibited ALK5 with IC50 value of 0.013 μM in a kinase assay and with IC50 values of 0.0165 and 0.0121 μM in HaCaT (3TP-luc) stable cells and 4T1 (3TP-luc) stable cells, respectively, in a luciferase assay. Selectivity profiling of 12b using a panel of 320 protein kinases revealed that it is a highly selective ALK5/ALK4 inhibitor. Pharmacokinetic study with 12b·HCl in rats showed an oral bioavailability of 51% with high systemic exposure (AUC) of 1426 ng × h/mL and maximum plasma concentration (Cmax) of 1620 ng/mL. Rational optimization of 6 has led to the identification of a highly potent, selective, and orally bioavailable ALK5 inhibitor 12b.
Continuous flow nucleophilic aromatic substitution with dimethylamine generated in situ by decomposition of DMF
Petersen, Trine P.,Larsen, Anders Foller,Ritzen, Andreas,Ulven, Trond
, p. 4190 - 4195 (2013/05/23)
A safe, practical, and scalable continuous flow protocol for the in situ generation of dimethylamine from DMF followed by nucleophilic aromatic substitution of a broad range of aromatic and heteroaromatic halides is reported.
2-ARYL- AND 2-HETEROARYLTHIAZOLYL COMPOUNDS, METHODS FOR THEIR PREPARATION AND USE THEREOF
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Page/Page column 53, (2009/10/22)
The present invention discloses fused bicyclic 2-aryl- or 2-heteroarylthiazolyl compounds and their pharmaceutically acceptable salts and esters thereof, which are useful for inhibiting the growth of cancerous cells, inhibiting human breast carcinoma tumo