54558-01-9Relevant academic research and scientific papers
Towards discovery of novel scaffold with potent antiangiogenic activity; design, synthesis of pyridazine based compounds, impact of hinge interaction, and accessibility of their bioactive conformation on VEGFR-2 activities
Jaballah, Maiy Y.,Serya, Rabah A. T.,Saad, Nasser,Khojah, Sohair M.,Ahmed, Marawan,Barakat, Khaled,Abouzid, Khaled A. M.
, p. 1573 - 1589 (2019/09/12)
Pyridazine scaffolds are considered privileged structures pertaining to its novelty, chemical stability, and synthetic feasibility. In our quest towards the development of novel scaffolds for effective vascular endothelial growth 2 (VEGFR-2) inhibition with antiangiogenic activity, four novel series of pyridazines were designed and synthesised. Five of the synthesised compounds; namely (8c, 8f, 15, 18b, and 18c) exhibited potent VEGFR-2 inhibitory potency (>80%); with IC50 values ranging from low micromolar to nanomolar range; namely compounds 8c, 8f, 15, 18c with (1.8 μM, 1.3 μM, 1.4 μM, 107 nM), respectively. Moreover, 3-[4-{(6-oxo-1,6-dihydropyridazin-3-yl)oxy}phenyl]urea derivative (18b) exhibited nanomolar potency towards VEGFR-2 (60.7 nM). In cellular assay, the above compounds showed excellent inhibition of VEGF-stimulated proliferation of human umbilical vein endothelial cells at 10 μM concentration. Finally, an extensive molecular simulation study was performed to investigate the probable interaction with VEGFR-2.
Synthesis and Bioevaluation of 3,6-Diaryl-[1,2,4]triazolo[4,3-b] Pyridazines as Antitubulin Agents
Xu, Qile,Wang, Yueting,Xu, Jingwen,Sun, Maolin,Tian, Haiqiu,Zuo, Daiying,Guan, Qi,Bao, Kai,Wu, Yingliang,Zhang, Weige
supporting information, p. 1202 - 1206 (2016/12/18)
A series of 3,6-diaryl-[1,2,4]triazolo[4,3-b]pyridazines were designed as a class of vinylogous CA-4 analogues. The easily isomerized (Z,E)-butadiene linker of vinylogous CA-4 was replaced by a rigid [1,2,4]triazolo[4,3-b]pyridazine scaffold. Twenty-one target compounds were synthesized and exhibited moderate to potent antiproliferative activity. The compound 4q with a 3-amino-4-methoxyphenyl moiety as the B-ring, comparable to CA-4 (IC50 = 0.009-0.012 μM), displayed the highly active antiproliferative activity against SGC-7901, A549, and HT-1080 cell lines with IC50 values of 0.014, 0.008, and 0.012 μM, respectively. Tubulin polymerization experiments indicated that 4q effectively inhibited tubulin polymerization, and immunostaining assay revealed that 4q significantly disrupted tubulin microtubule dynamics. Moreover, cell cycle studies revealed that compound 4q dramatically arrested cell cycle progression at G2/M phase in A549 cells. Molecular modeling studies showed that 4q could bind to the colchicine binding site on microtubules.
PYRIDAZINONE DERIVATIVES
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Page/Page column 21, (2010/08/03)
Compounds of the formula (I), in which R1, R2 and R3 have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours.
INHIBITORS OF C-MET AND USES THEREOF
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Page/Page column 54, (2008/06/13)
The present invention relates to compounds and methods use as inhibitors of c-Met. Certain compounds of the subject invention have the following structural formula (I). Other compounds of the subject invention have structural formulas as defined herein. A
One-pot preparation of 6-substituted 3(2H)-pyridazinones from ketones
Coates,McKillop
, p. 334 - 342 (2007/10/02)
A one-pot process for the preparation of 6-phenyl-3(2H)-pyridazinone from acetophenone and glyoxylic acid has been investigated and shown to have wide utility in the preparation of 6- and 5,6-substituted 3(2H)-pyridazinones. Limitations to the process encountered with 2'-hydroxyacetophenone and with basic hetero-aromatic ketones have been overcome, and the processes described offer the rapid and efficient synthesis of many 6-substituted pyridazinones from readily available ketones.
QUANTITATIVE DETERMINATION OF THE ELECTRONIC EFFECTS OF 3- AND 4-PYRIDAZINYL GROUPS FROM NMR SPECTRAL DATA FOR ISOMERIC AMINOPHENYL- AND PHENYLPYRIDAZINES
Shkurko, O. P.,Kuznetsov, S. A.,Denisov, A. Yu.,Mamaev, V. P.
, p. 763 - 770 (2007/10/02)
The previously unknown aminophenylpyridazines were synthesized.The inductive and resonance constants of 3- and 4-pyridazinyl groups were calculated on the basis of 1H and 13C NMR spectral data for isomeric aminophenyl- and phenylpyridazines in dimethyl sulfoxide (DMSO).
Synthesis and Anxiolytic Activity of 6-(Substituted-phenyl)-1,2,4-triazolopyridazines
Albright, J. D.,Moran, D. B.,Wright, W. B.,Collins, J. B.,Beer, B.,et al.
, p. 592 - 600 (2007/10/02)
The synthesis of a series of 6-(substituted-phenyl)-1,2,4-triazolopyridazines (VIII) is reported.Some of these derivatives show activity in tests predictive of anxiolytic activity (a) protection against pentylenetetrazole-induced convulsions; (b)
Method for treating anxiety in mammals
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, (2008/06/13)
This disclosure describes compositions of matter useful as anxiolytic agents and the method of meliorating anxiety in mammals therewith; the active ingredients of said compositions of matter being certain substituted 6-phenyl-1,2,4-triazolo[4,3-b]pyridazines or the pharmacologically acceptable acid-addition salts thereof.
6-Phenyl-1,2,4-triazolo[4,3-b]pyridazine hypotensive agents
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, (2008/06/13)
This disclosure describes novel substituted 6-phenyl-1,2,4-triazolo[4,3-b]pyridazines useful as hypotensive agents.
