41222-60-0Relevant articles and documents
METHOD FOR PRODUCING OXAZOLE COMPOUND
-
, (2014/03/25)
An object of the present invention is to provide a novel method for producing an oxazole compound. The invention relates to a method for producing a compound represented by formula (1): wherein R1 is lower alkyl group or halogen substituted lower alkyl group, R2 is lower alkyl group, R5 is lower alkyl group, R11 is lower alkyl group, halogen substituted lower alkyl group or a group represented by formula: -CY2COOR12, wherein Y is a halogen atom, R12 is an alkali metal atom or lower alkyl group, Ar1 is phenyl group substituted with lower alkyl group, etc., or pyridyl group substituted with lower alkyl group, etc., X2, X3 and X9 are the same or different and are halogen atoms, X4 is a leaving group, and M is an alkali metal atom.
Synthesis and biological evaluation of novel 4-indolyl-5-phenyl(indolyl)-1, 2-dihydropyrazol-3-ones as glycogen synthase kinase-3β (GSK-3β) inhibitors
Yin, Hong,Shangguan, Yingying,Sui, Fengying,Yang, Xinji,Song, Guojie
, p. 780 - 788,9 (2020/09/15)
Nineteen novel 4-indolyl-5-phenyl(indolyl)-1,2-dihydropyrazol-3-ones were synthesized and evaluated for their GSK-3β inhibitory activity. Half of the tested compounds showed moderate GSK-3β inhibitory activity. Preliminary structure-activity relationships were discussed, which showed that the presence of 3,4,5-trimethoxy group on the benezene ring enhanced potency while the existence of an electron-withdrawing group at the 4-position of the benezene ring deceased activity. Compounds 11c and 14, the most potent compounds with IC50 values of 9.28 and 8.98 μM, respectively, would be promising candidates for further development of novel GSK-3β inhibitors.
Pharmacological validation of trypanosoma brucei phosphodiesterases B1 and B2 as druggable targets for African sleeping sickness
Bland, Nicholas D.,Wang, Cuihua,Tallman, Craig,Gustafson, Alden E.,Wang, Zhouxi,Ashton, Trent D.,Ochiana, Stefan O.,McAllister, Gregory,Cotter, Kristina,Fang, Anna P.,Gechijian, Lara,Garceau, Norman,Gangurde, Rajiv,Ortenberg, Ron,Ondrechen, Mary Jo,Campbell, Robert K.,Pollastri, Michael P.
experimental part, p. 8188 - 8194 (2012/01/13)
Neglected tropical disease drug discovery requires application of pragmatic and efficient methods for development of new therapeutic agents. In this report, we describe our target repurposing efforts for the essential phosphodiesterase (PDE) enzymes TbrPDEB1 and TbrPDEB2 of Trypanosoma brucei, the causative agent for human African trypanosomiasis (HAT). We describe protein expression and purification, assay development, and benchmark screening of a collection of 20 established human PDE inhibitors. We disclose that the human PDE4 inhibitor piclamilast, and some of its analogues, show modest inhibition of TbrPDEB1 and B2 and quickly kill the bloodstream form of the subspecies T. brucei brucei. We also report the development of a homology model of TbrPDEB1 that is useful for understanding the compound-enzyme interactions and for comparing the parasitic and human enzymes. Our profiling and early medicinal chemistry results strongly suggest that human PDE4 chemotypes represent a better starting point for optimization of TbrPDEB inhibitors than those that target any other human PDEs.
