19093-39-1Relevant articles and documents
Synthesis and biological evaluation of optimized inhibitors of the mitotic kinesin Kif18A
Braun, Joachim,M?ckel, Martin M.,Strittmatter, Tobias,Marx, Andreas,Groth, Ulrich,Mayer, Thomas U.
, p. 554 - 560 (2015)
The mitotic spindle, a highly dynamic structure composed of microtubules, mediates the segregation of the previously duplicated genome into the two nascent daughter cells. Errors in this process contribute to pathology including tumor formation. Key for the shape and function of the mitotic spindle are kinesins, molecular motor proteins that convert chemical energy into mechanical work. Due to their fast mode of action, small molecules are valuable tools to dissect the dynamic functions of kinesins during mitosis. In this study, we report the identification of optimized small molecule inhibitors of the mitotic kinesin Kif18A. Using BTB-1, the first identified Kif18A inhibitor, as a lead compound, we synthesized a collection of derivatives. We demonstrate that some of the synthesized derivatives potently inhibited the ATPase activity of Kif18A with a half maximal inhibitory concentration (IC50) value in the low micromolar range. In vitro analysis of a panel of Kif18A-related kinesins revealed that the two most potent compounds show improved selectivity compared to BTB-1. Structure-activity relationship studies identified substituents mediating undesired inhibitory effects on microtubule polymerization. In summary, our study provides key insights into the mechanism of action of BTB-1 and its analogs, which will have a great impact on the further development of highly selective and bioactive Kif18A inhibitors. Since Kif18A is frequently overexpressed in solid tumors, such compounds are not only of great interest for basic research but also have the potential to open up new strategies for the treatment of human diseases.
H2O2/Tf2O system: An efficient oxidizing reagent for selective oxidation of sulfanes
Khodaei, Mohammad Mehdi,Bahrami, Kiumars,Karimi, Ahmad
, p. 1682 - 1684 (2008/12/21)
A versatile procedure for the oxidation of sulfanes to sulfoxides without any overoxidation to sulfones has been reported. It is noteworthy that the reaction tolerates oxidatively sensitive functional groups and that the sulfur atom is selectively oxidize
Carboxy pyridinium bromide perbromide reagents, part I: Selective oxidation of thiols and sulfides
Lakouraj, Moslem M.,Ghodrati, Keivan
experimental part, p. 1432 - 1439 (2009/05/07)
Efficient and convenient oxidation of aliphatic and aromatic thiols to disulfides and of sulfides to sulfoxides with pyridinium hydrobromide perbromide (PHBP), nicotinic acid hydrobromide perbromide (NAHBP), and 2,6-dicarboxy pyridinium hydrobromide perbromide (DCPHBP) in a solvent or under solvent free conditions and at ambient temperature is introduced. Copyright Taylor & Francis Group, LLC.
2,6-Dicarboxypyridinium chlorochromate: An efficient and selective reagent for the oxidation of thiols to disulfides and sulfides to sulfoxides
Tajbakhsh, Mahmood,Hosseinzadeh, Rahman,Shakoori, Alireza
, p. 1889 - 1893 (2007/10/03)
2,6-Dicarboxypyridinium chlorochromate (2,6-DCPCC) was found to be an efficient reagent for the conversion of thiols to disulfides and sulfides to sulfoxides under neutral and anhydrous conditions in good to excellent yields. Selective oxidation of thiols in the presence of sulfides at room temperature is also observed with this reagent.
VARIATION OF THE VALENCE OF SULFUR IN SUBSTITUTED 2,4-DINITROPHENYL PHENYL SULFOXIDES IN REARRANGEMENT PROCESSES
Efremov, Yu. A.,Popova, A. G.,Khmel'nitskii, R. A.,Kaminskii, A. Ya,Fedyainov, N. V.
, p. 944 - 949 (2007/10/02)
The oxidation of the bridging sulfur atom in diphenyl sulfides, leading to the formation of sulfoxides and sulfones, was investigated.The various rearrangement processes which occur in substituted 2,4-dinitrophenyl phenyl sulfoxides during electron impact and lead to the appearance of characteristic fragment ions were demonstrated.The effect of the nature of substituents on the main directions in mass-spectrometric dissociation was investigated, and a correlation was obtained between log Z'/Z for the fragment due to elimination of the bridging SO group from the molecular ion and the Hammett ? constants.
