- Ureido-Pyridazinone Derivatives: Insights into the Structural and Conformational Properties for STAT3 Inhibition
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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.
- Meneghetti, Fiorella,Villa, Stefania,Masciocchi, Daniela,Barlocco, Daniela,Toma, Lucio,Han, Dong-Cho,Kwon, Byoung-Mog,Ogo, Naohisa,Asai, Akira,Legnani, Laura,Gelain, Arianna
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p. 4907 - 4912
(2015/08/03)
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- Methylation of 5-Aldehydo-6-arylpyridazin-3(2H)-ones via Reaction with Dimethyl and Pentamethyl Cuprates
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Me5Cu3Li2 in ether or ether-pentane mixtures, converts the title compounds efficiently into the corresponding 4-methyl derivatives (5) via conjugate methylation of either α,β-unsaturated aldehyde or N=C-C=C system, together with ca. 20percent of 1,2 adduc
- Shams, Nabil A.
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p. 536 - 542
(2007/10/02)
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