29602-39-9Relevant articles and documents
Discovery of nitroaryl urea derivatives with antiproliferative properties
Wróbel, Tomasz M.,Kie?bus, Micha?,Kaczor, Agnieszka A.,Kry?tof, Vladimír,Karczmarzyk, Zbigniew,Wysocki, Waldemar,Fruziński, Andrzej,Król, Sylwia K.,Grabarska, Aneta,Stepulak, Andrzej,Matosiuk, Dariusz
, p. 608 - 618 (2016)
A series of urea derivatives bearing nitroaryl moiety has been synthesized and assayed for their potential antiproliferative activities. Some of the tested compounds displayed activity in RK33 laryngeal cancer cells and TE671 rhabdomyosarcoma cells while being generally less toxic to healthy HSF human fibroblasts cells. One compound was demonstrated to be a moderate CDK2 inhibitor with IC50 = 14.3 μM. Its structure was solved by an X-ray crystallography and molecular modelling was performed to determine structure-activity relationship. Obtained compounds constitute novel structures and generally demonstrated greater cytotoxicity in comparison to cisplatin. This study offers new structural motifs with potential for further development.
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.
