103962-24-9Relevant articles and documents
Synthesis, Binding Mode, and Antihyperglycemic Activity of Potent and Selective (5-Imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine Inhibitors of Glycogen Synthase Kinase 3
Wagman, Allan S.,Boyce, Rustum S.,Brown, Sean P.,Fang, Eric,Goff, Dane,Jansen, Johanna M.,Le, Vincent P.,Levine, Barry H.,Ng, Simon C.,Ni, Zhi-Jie,Nuss, John M.,Pfister, Keith B.,Ramurthy, Savithri,Renhowe, Paul A.,Ring, David B.,Shu, Wei,Subramanian, Sharadha,Zhou, Xiaohui A.,Shafer, Cynthia M.,Harrison, Stephen D.,Johnson, Kirk W.,Bussiere, Dirksen E.
, p. 8482 - 8514 (2017/11/03)
In an effort to identify new antidiabetic agents, we have discovered a novel family of (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine analogues which are inhibitors of human glycogen synthase kinase 3 (GSK3). We developed efficient synthetic routes to explore a wide variety of substitution patterns and convergently access a diverse array of analogues. Compound 1 (CHIR-911, CT-99021, or CHIR-73911) emerged from an exploration of heterocycles at the C-5 position, phenyl groups at C-4, and a variety of differently substituted linker and aminopyridine moieties attached at the C-2 position. These compounds exhibited GSK3 IC50s in the low nanomolar range and excellent selectivity. They activate glycogen synthase in insulin receptor-expressing CHO-IR cells and primary rat hepatocytes. Evaluation of lead compounds 1 and 2 (CHIR-611 or CT-98014) in rodent models of type 2 diabetes revealed that single oral doses lowered hyperglycemia within 60 min, enhanced insulin-stimulated glucose transport, and improved glucose disposal without increasing insulin levels.
AZOLE DERIVATIVES
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, (2008/06/13)
Azole derivatives of the formulas R1-CR2R3-CHR4-CR5R6-R7 are described; wherein R1 is a heterocyclyl radicla selected from 1,2,4-triazolyl, optionally-substituted imidazolyl, pyridyl and pyrimidinyl radicals; R2 and R3, which may be the same or differen
Synthesis and Antifungal Activity of a Series of Novel 1,2-Disubstituted Propenones
Ogata, Masaru,Matsumoto, Hiroshi,Kida, Shiro,Shimizu, Sumio,Tawara, Katsuya,Kawamura, Yoshimi
, p. 1497 - 1502 (2007/10/02)
To find an antifungal agent other than those of the imidazole and triazole series, a new class of 1,2-disubstituted propenones I and II was prepared and tested for antifungal activity.Comparison of the structure-activity relationships showed that the conjugated structure of carbonyl and exomethylene groups in I and II plays an important role in potent antifungal acivity.However, it is noteworthy that compounds 53, 54, and 56, which have a hydroxymethyl or methoxymethyl group instead of an exo-methylene group in I, also showed potent activity.Although many compounds exhibited strong antifungal activity in vitro, none showed activity in vivo of oral efficacy against subacute systemic candidiasis in mice. '
