Bavetsias, Vassilios; Large, Jonathan M.; Sun, Chongbo; Bouloc, Nathalie; Kosmopoulou, Magda; Matteucci, Mizio; Wilsher, Nicola E.; Martins, Vanessa; Reynisson, Johannes; Atrash, Butrus; Faisal, Amir; Urban, Frederique; Valenti, Melanie; Brandon, Alexis de Haven; Box, Gary; Raynaud, Florence I.; Workman, Paul; Eccles, Suzanne A.; Bayliss, Richard; Blagg, Julian; Linardopoulos, Spiros; McDonald, Edward published the artcile< Imidazo[4,5-b]pyridine Derivatives As Inhibitors of Aurora Kinases: Lead Optimization Studies toward the Identification of an Orally Bioavailable Preclinical Development Candidate>, Quality Control of 188577-68-6, the main research area is imidazopyridine derivative arsenic inhibitor Aurora kinase orally bioavailable development.
Lead optimization studies using an imidazo[4,5-b]pyridinylpiperazine as the starting point led to a new class of imidazo[4,5-b]pyridine-based inhibitors of Aurora kinases that possessed the 1-benzylpiperazinyl motif at the 7-position, and displayed favorable in vitro properties. Cocrystn. of Aurora-A with a morpholinylmethylphenylimidazopyridinyl chlorobenzyl piperazine (CCT137444) provided a clear understanding into the interactions of this novel class of inhibitors with the Aurora kinases. Subsequent physicochem. property refinement by the incorporation of solubilizing groups led to the identification of 3-((4-(6-bromo-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)methyl)-5-methylisoxazole (CCT137690)(I) which is a potent inhibitor of Aurora kinases (Aurora-A IC50 = 0.015±0.003 μM, Aurora-B IC50 = 0.025 μM, Aurora-C IC50 = 0.019 μM). I is highly orally bioavailable, and in in vivo efficacy studies it inhibited the growth of SW620 colon carcinoma xenografts following oral administration with no observed toxicities as defined by body weight loss.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 188577-68-6 belongs to class pyridine-derivatives, and the molecular formula is C5H4Cl2N2, Quality Control of 188577-68-6.