94360-65-3Relevant academic research and scientific papers
High-Throughput Screening and Hit Validation of Extracellular-Related Kinase 5 (ERK5) Inhibitors
Myers, Stephanie M.,Bawn, Ruth H.,Bisset, Louise C.,Blackburn, Timothy J.,Cottyn, Betty,Molyneux, Lauren,Wong, Ai-Ching,Cano, Celine,Clegg, William,Harrington, Ross. W.,Leung, Hing,Rigoreau, Laurent,Vidot, Sandrine,Golding, Bernard T.,Griffin, Roger J.,Hammonds, Tim,Newell, David R.,Hardcastle, Ian R.
supporting information, p. 444 - 455 (2016/08/16)
The extracellular-related kinase 5 (ERK5) is a promising target for cancer therapy. A high-throughput screen was developed for ERK5, based on the IMAP FP progressive binding system, and used to identify hits from a library of 57-617 compounds. Four distinct chemical series were evident within the screening hits. Resynthesis and reassay of the hits demonstrated that one series did not return active compounds, whereas three series returned active hits. Structure-activity studies demonstrated that the 4-benzoylpyrrole-2-carboxamide pharmacophore had excellent potential for further development. The minimum kinase binding pharmacophore was identified, and key examples demonstrated good selectivity for ERK5 over p38α kinase.
CYCLIZATION OF NITRILES. XVII. METHODS FOR THE PRODUCTION OF 4,6-DIARYL-3-CYANO-2(1H)-PYRIDINETHIONES AND THEIR MASS-SPECTROMETRIC INVESTIGATION
Promonenkov, V. K.,Shestopalov, A. M.,Sharanin, Yu. A.,Litvinov, V. P.,Rodinovskaya, L. A.,et al.
, p. 1797 - 1802 (2007/10/02)
The boundaries of the methods for the synthesis of 2(1H)-pyridinethiones were extended.The reactions of 3-aroyl-2-aryl- and 3-aroyl-2-aryl-1-bromo-1,1-dicyanopropanes with sodium and morpholinium hydrosulfides and thiourea and of arylidenecyanothioacetamides and 3-aryl-2,4,4-tricyano-3-butenethioamides with acetophenone, and 1-(1-piperidino)-1-phenylethylene, and also the reactions of monothiodibenzoylmethane and 1,3-diphenyl-1-(1-piperidino)-1-propene-3-one with cyanothioacetamide, leading to 4,6-diaryl-3-cyano-2(1H)-pyridinethiones, were investigated.The use of substituted cyanothioacetamides seems most promising.Mass-spectrometric investigation of the obtained thiones showed that the main direction in the dissociation of their molecular ions is the elimination of the H, HS., and CS particles with the formation of the thiazepinium and pyridinium ions and the corresponding radical-cation of pyrrole.
CYCLIZATION OF NITRILES. IX. SYNTHESES BASED ON 2-ARYL-3-AROYL-1,1-DICYANOPROPANES
Shestopalov, A. M.,Promonenkov, V. K.,Sharanin, Yu. A.,Rodinovskaya, L. A.,Sharanin, S. Yu.
, p. 1382 - 1401 (2007/10/02)
2-Aryl-3-aroyl-1,1-dicyanopropanes and 2-aryl-3-aroyl-1-bromo-1,1-dicyanopropanes were synthesized from chalcones and malononitrile and were converted into 4,6-diaryl-2-bromo-3-cyanopyridines and 3-cyano-2(1H)-pyridinethiones.The 2-aryl-3-aroyl-1-bromo-1,1-dicyanopropanes proved convenient intermediates for the production of the corresponding cyclopropanes and other compounds.By their reaction with urea a new method was developed for the production of substituted 3-cyano-2(1H)-pyridinethiones.The 2-bromo-3-cyanopyridines contain a mobile bromine atom readily exchanged for the various nucleophilic residues of alcohols and amines and for iodide, and cyano and thiocyanato groups.The 3-cyano-2(1H)-pyridinethiones were used in the synthesis of 3-aminothienopyridines through the isolated 2-Z-methylthio-3-cyanopyridines.
