Identification of Inhibitors of Checkpoint Kinase 1 through Template Screening was written by Matthews, Thomas P.;Klair, Suki;Burns, Samantha;Boxall, Kathy;Cherry, Michael;Fisher, Martin;Westwood, Isaac M.;Walton, Michael I.;McHardy, Tatiana;Cheung, Kwai-Ming J.;Van Montfort, Rob;Williams, David;Aherne, G. Wynne;Garrett, Michelle D.;Reader, John;Collins, Ian. And the article was included in Journal of Medicinal Chemistry in 2009.SDS of cas: 173341-02-1 This article mentions the following:
Checkpoint kinase I (CHKI) is an oncol. target of significant current interest. Inhibition of CHK1 abrogates DNA damage-induced cell cycle checkpoints and sensitizes p53 deficient cancer cells to genotoxic therapies. Using template screening, a fragment-based approach to small mol. hit generation, we have identified multiple CHK1 inhibitor scaffolds suitable for further optimization. The sequential combination of in silico low mol. weight template selection, a high concentration biochem. assay and hit validation through protein-ligand X-ray crystallog. provided 13 template hits from an initial in silico screening library of ca. 15000 compounds The use of appropriate counter-screening to rule out nonspecific aggregation by test compounds was essential for optimum performance of the high concentration bioassay. One low mol. weight, weakly active purine template hit was progressed by iterative structure-based design to give submicromolar pyrazolopyridines with good ligand efficiency and appropriate CHK1-mediated cellular activity in HT29 colon cancer cells. In the experiment, the researchers used many compounds, for example, tert-Butyl (morpholin-2-ylmethyl)carbamate (cas: 173341-02-1SDS of cas: 173341-02-1).
tert-Butyl (morpholin-2-ylmethyl)carbamate (cas: 173341-02-1) belongs to esters. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Esters contain a carbonyl center, which gives rise to 120鎺?C閳ユ弲閳ユ彊 and O閳ユ弲閳ユ彊 angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C閳ユ彊閳ユ弲 bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. SDS of cas: 173341-02-1
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics