- 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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- PYRROLIDINYL UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS
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Compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts, or solvates or prodrugs thereof, where R1, R2, Ra, Rb, Rc, Rd, X, Ring B, and Ring C are as defined herein, and wherein Ring B moiety and the NH-C(=X)-NH moiety are in the trans configuration, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis and pelvic pain syndrome.
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- Pyridazines. XV. Synthesis of 6-aryl-5-amino-3(2H)-pyridazinones as potential platelet aggregation inhibitors
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Several 3(2H)-pyridazinones with amino groups at the 5-position of the pyridazine nucleus have been prepared. The 6-aryl-5-halo-3(2H)-pyridazinones obtained from mucochloric and mucobromic acid lead to the corresponding 5- alkylamino-3(2H)-pyridazinones,
- Estevez, Isabel,Ravina, Enrique,Sotelo, Eddy
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p. 1421 - 1428
(2007/10/03)
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- PYRIDAZINE DERIVATIVES, IX. SYNTHESIS OF 2H-PYRIDAZIN-3-ONES WITH AROYLPIPERAZINYL GROUPS
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Several 2H-pyridazin-3-ones with phenyl- or 2-furoylpiperazinyl group, have been prepared. 6-Phenyl-5-(N4-aroyl-N1-piperazinyl)-2H-pyridazin-3-ones were obtained by nucleophilic substitution of the chlorine atom of 6-phenyl-5-chloro-
- Ravina, Enrique,Teran, Carmen,Santana, Lourdes,Garcia, Neftali,Estevez, Isabel
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p. 1967 - 1974
(2007/10/02)
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