105537-49-3Relevant 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.
Copper-catalyzed aerobic dehydrogenation of C-C to C=C bonds in the synthesis of pyridazinones
Liang, Lei,Yang, Guanyu,Xu, Fengrong,Niu, Yan,Sun, Qi,Xu, Ping
supporting information, p. 6130 - 6136 (2013/09/24)
A simple and efficient procedure for the synthesis of pyridazin-3(2H)-ones through copper-catalyzed dehydrogenation of a single C-C bond of 4,5-dihydropyridazin-3(2H)-ones to a C=C bond with oxygen as the terminal oxidant is described. Functional groups including hydroxy, carboxylic, bromo, chloro, cyano, nitro and alkoxy were all tolerated under the reaction conditions. Moreover, this methodology was applied to the preparation of a series of structurally similar N-substituted 6-phenylpyridazinone compounds containing fluorine. The dehydrogenation reactions exhibit good yields and selectivity. Copper-catalyzed dehydrogenation of a C-C bond of 4,5-dihydropyridazinones to a C=C bond with oxygen as the terminal oxidant is described. Various functional groups were tolerated under the reaction conditions. The method was also applied to the preparation of a series of N-substituted 6-phenylpyridazinones containing fluoride. The dehydrogenation reactions exhibit good yields and selectivity.
Unexpected C-C bond cleavage: A route to 3,6-diarylpyridazines and 6-arylpyridazin-3-ones from 1,3-dicarbonyl compounds and methyl ketones
Gao, Qinghe,Zhu, Yanping,Lian, Mi,Liu, Meicai,Yuan, Jingjing,Wu, Anxin,Yin, Guodong
, p. 9865 - 9870,6 (2012/12/12)
An unexpected C-C bond cleavage has been revealed in the absence of metal. This observation has been exploited to develop an efficient approach toward 3,6-diarylpyridazines and 6-arylpyridazin-3-ones from simple and commercially available 1,3-dicarbonyl compounds and methyl ketones.
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.
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.
Synthesis and Structure-Activity Relationships of Series of Aminopyridazine Derivatives of γ-Aminobutyric Acid Acting as Selective GABA-A Antagonists
Wermuth, Camille-Georges,Bourguignon, Jean-Jacques,Schlewer, Gilbert,Gies, Jean-Pierre,Schoenfelder, Angele,et al.
, p. 239 - 249 (2007/10/02)
We have recently shown that an aryloaminopyridazine derivarive of GABA, SR 95103 , is a selective and competitive GABA-A receptor antagonist.In order to further explore the structural requirements for GABA receptor affinity, we synthesized a series of 38 compounds by attaching various pyridazinic structures to GABA or GABA-like side chains.Most of the compounds displaced GABA from rat brain membranes.All the active compounds antagonized the GABA-elicited enhancement of diazepam binding, strongly suggesting that all these compounds are GABA-A receptor antagonists.None of the compounds that displaced GABA from rat brain membranes interacted with other GABA recognition sites (GABA-B receptor, GABA uptake binding site, glutamate decarboxylase, GABA-transaminase).They did not interact with the Cl- ionophore associated with the GABA-A receptor and did not interact with the benzodiazepine, strychnine, and glutamate binding sites.Thus these compounds appear to be specific GABA-A receptor antagonists.In terms of structure-activity, it can be concluded that a GABA moiety bearing a positive charge is necessary for optimal GABA-A receptor recognition.Additional binding sites are tolerated only if they are part of a charge-delocalized amidinic or guanidinic system.If this delocalization is achieved by linking a butyric acid moiety to the N(2) nitrogen of a 3-aminopyridazine, GABA-antagonistic character is produced.The highest potency (ca.250 times bicuculline) was observed when an aromatic ? system, bearing electron-donating substituents, was present on the 6-position of the pyridazine ring.
