Ureido-pyridazinone derivatives: Insights into the structural and conformational properties for STAT3 inhibition = 피리다지논 계열의 스탯3 저해제의 구조-활성 연구

Cited 9 time in scopus
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Title
Ureido-pyridazinone derivatives: Insights into the structural and conformational properties for STAT3 inhibition = 피리다지논 계열의 스탯3 저해제의 구조-활성 연구
Author(s)
F Meneghetti; S Villa; D Masciocchi; D Barlocco; L Toma; Dong Cho HanByoung-Mog Kwon; N Ogo; A Asai; L Legnani; A Gelain
Bibliographic Citation
European Journal of Organic Chemistry, vol. 2015, no. 22, pp. 4907-4912
Publication Year
2015
Abstract
Three new ureido-pyridazinone derivatives, which are structurally related to the known STAT3 inhibitor AVS-0288, were designed by taking into account the structure-activity relationships determined for several ureido-oxadiazole derivatives previously studied by our group. Their synthesis was first attempted through suitable 5-aminopyridazinone intermediates (6a and 6b), which molecular structures were confirmed by means of X-ray diffraction data on 6a. Amine functionalization was unsuccessful, therefore, an alternative method was devised. Dual-luciferase and AlphaScreen-based assays were used to test their activity. The obtained data were rationalized on the basis of a modeling study, which focused our attention on the geometrical preferences of the ureido moiety. Computational results seem to indicate that both the 1,2,5-oxadiazole ring and the extended ZZ arrangement are essential and probably act in a synergistic way to confer significant activity against STAT3.
Keyword
CancerConformation analysisInhibitorsMedicinal chemistryProteinsSignal transduction
ISSN
1434-193X
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/ejoc.201500599
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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