17284-97-8Relevant articles and documents
Structurally diverse copper(ii) complexes with pyridazine-integrated with pyrazine-Schiff base ligand featuring an easily lost proton in the hydrazone backbone
Cao, Jing,Liu, Jia-Cheng,Deng, Wen-Ting,Jin, Neng-Zhi
, p. 6359 - 6367 (2013)
To probe the coordination approach of pyridazine and pyrazine ligands, five new complexes of [CuII2L2Cl2] (1), [CuII(L-H)(NO3)(H2O)2](NO 3)(H2O) (2), {[CuII(L-H)(H2O)] (ClO4)2(H2O)}n (3), [Cu II2L2(OH)](NO3)(H2O) 2 (4), [CuII2L2(OH)](ClO 4) (5) based on Schiff base ligand (E)-3-chloro-6-[2-(pyrazin-2- ylmethylene)hydrazinyl]pyridazine (HL) bearing pyridazinyl and pyrazinyl groups have been synthesized and characterized by IR spectra, elemental analyses, the bond valence sum (BVS) analyses, powder X-ray diffraction (PXRD) analyses, X-ray single crystal diffraction and density function theory calculations. The structures of 1, 2 and 3 suggest that the second nitrogen donors of the pyrazinyl unit can link with other metal ions to construct a higher dimensional architecture by the reaction of HL with Cu(ClO4)2 [CuCl2 for 1, Cu(NO3)2 for 2 and Cu(ClO 4)2 for 3]. The structures of 4 and 5 indicate that additional donor units of the pyridazinyl chromophore can bind multiple metal ions to form a multi-metallic cluster, when the protons of the hydrazone backbones are abstracted in the presence of triethylamine to strengthen the coordination behavior of the second nitrogen atom. However, for 1, the protons of the hydrazone backbone are lost with or without triethylamine and the additional nitrogen atoms of the pyrazinyl and pyridazinyl groups are not found to connect to other metal ions, which can probably be assigned to the strong coupling effect of chlorine ions. Magnetic measurements display weak antiferromagnetic coupling between the copper(ii) ions in 1 and 5, and ferromagnetic coupling in 3. In addition, the antioxidant activities of HL and 1-5 were also studied.
Pyridazine-versus pyridine-based tridentate ligands in first-row transition metal complexes
Gruenwald, Katrin R.,Volpe, Manuel,Cias, Pawel,Gescheidt, Georg,Moesch-Zanetti, Nadia C.
, p. 7478 - 7488 (2011)
A series of first-row transition metal complexes with the unsymmetrically disubstituted pyridazine ligand picolinaldehyde (6-chloro-3-pyridazinyl) hydrazone (PIPYH), featuring an easily abstractable proton in the backbone, was prepared. Ligand design was inspired by literature-known picolinaldehyde 2-pyridylhydrazone (PAPYH). Reaction of PIPYH with divalent nickel, copper, and zinc nitrates in ethanol led to complexes of the type [CuII(PIPYH) (NO3)2] (1) or [M(PIPYH)2](NO3) 2 [M = NiII (2) or ZnII (3)]. Complex synthesis in the presence of triethylamine yielded fully- or semideprotonated complexes [CuII(PIPY)(NO3)] (4), [NiII(PIPYH)(PIPY)] (NO3) (5), and [ZnII(PIPY)2] (6), respectively. Cobalt(II) nitrate is quantitatively oxidized under the reaction conditions to [CoIII(PIPY)2](NO3) (7) in both neutral and basic media. X-ray diffraction analyses reveal a penta- (1) or hexa-coordinated (2, 3, and 7) metal center surrounded by one or two tridentate ligands and, eventually, κ-O,O′ nitrate ions. The solid-state stoichiometry was confirmed by electron impact (EI) and electrospray ionization (ESI) mass spectrometry. The diamagnetic complexes 5 and 6 were subjected to 1H NMR spectroscopy, suggesting that the ligand to metal ratio remains constant in solution. Electronic properties were analyzed by means of cyclic voltammetry and, in case of copper complexes 1 and 4, also by electron paramagnetic resonance (EPR) spectroscopy, showing increased symmetry upon deprotonation for the latter, which is in accordance with the proposed stoichiometry [Cu II(PIPY)(NO3)]. Protic behavior of the nickel complexes 2 and 5 was investigated by UV/vis spectroscopy, revealing high π-backbonding ability of the PIPYH ligand resulting in an unexpected low acidity of the hydrazone proton in nickel complex 2.
Machine-assisted synthesis of modulators of the histone reader BRD9 using flow methods of chemistry and frontal affinity chromatography
Guetzoyan, Lucie,Ingham, Richard J.,Nikbin, Nikzad,Rossignol, Julien,Wolling, Michael,Baumert, Mark,Burgess-Brown, Nicola A.,Strain-Damerell, Claire M.,Shrestha, Leela,Brennan, Paul E.,Fedorov, Oleg,Knapp, Stefan,Ley, Steven V.
, p. 540 - 546 (2014)
A combination of conventional organic synthesis, remotely monitored flow synthesis and bioassay platforms, were used for the evaluation of novel inhibitors targeting bromodomains outside the well-studied bromodomain and extra terminal (BET) family, here e
Synthesis and identification of novel pyridazinylpyrazolone based diazo compounds as inhibitors of human islet amyloid polypeptide aggregation
Farrukh, Syed Usama Bin,Javed, Ibrahim,Ather, Abdul Qayyum,Emwas, Abdul-Hamid,Alazmi, Meshari,Gao, Xin,Chotana, Ghayoor Abbas,Davis, Thomas P.,Ke, Pu Chun,Saleem, Rahman Shah Zaib
, p. 339 - 346 (2019)
We have carried out a docking inspired synthesis and screening of a library of diazenyl-derivatives of pyridazinylpyrazolone molecules for their ability to modulate the amyloidogenic self-assembly of human islet amyloid polypeptide (hIAPP). hIAPP is a 37-residue peptide which is involved in glycemic control along with insulin. Its extracellular fibrillar assemblies in pancreatic β-cells are responsible for type 2 diabetes. A three-step synthetic scheme was used to prepare these novel compounds using 2-(6-chloropyridazin-3-yl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one as a key intermediate that was reacted with various diazo electrophiles to generate a library of compounds with yields ranging from 64 to 85%. The effect of the compounds on hIAPP amyloid fibril formation was evaluated with a thioflavin T (ThT) fluorescence-based kinetic assay. Furthermore, TEM imaging was carried out to corroborate the interactions of the compounds with hIAPP and subsequent hIAPP inhibition at the different level of fibrillization. The CD spectroscopy showed that upon incubation with SSE15314 for 12 h, the percentage of α-helices was maintained to a level of hIAPP at 0 h. The current study presents identification and characterization of SSE15314 as the hit, which completely inhibited the fibril formation and can be further optimized into a lead compound.
Multinuclear magnetic resonance study of the structure and tautomerism of azide and iminophosphorane derivatives of chloropyridazines
Cmoch, Piotr
, p. 507 - 516 (2002)
Some azido- and iminophosphorane derivatives of 3,6-dichloro- and 3,4,5,6-tetrachloropyridazine were synthesized and studied by means of NMR measurements. Based on multinuclear data (chemical shifts, coupling constants) for compounds containing the azide group, no potentially possible tetrazole-azide equilibrium can be observed, even under acidic conditions. An unusual substitution of a chlorine atom (in position 4) of tetrachloropyridazine in the reaction with hydrazine was demonstrated by NMR measurements of two newly synthesized compounds containing azido- and iminophosphorane groups. Using multinuclear magnetic resonance data, the sites of ethylation and protonation of azido- and iminophosphorane derivatives of chloropyridazines were established. In the case of the tetrazolopyridazines, ethylation occurs at the N1′ and N2′ atoms, whereas for monocyclic compounds it takes place at the N1 and/or N2 atoms of the pyridazine ring. Preferred sites of protonation are the N1′ atom of the tetrazole ring and the N1 atom of the pyridazine ring. Moreover, the structures of potassium salts of 6-(3-cyano-1-triazeno)tetrazolo[1,5-b] pyridazine and its amido derivative were established using NMR data, especially 15N NMR chemical shifts. Copyright
Synthesis, structural analysis, Hirshfeld surface analysis, DFT calculations, in vitro and docking study on antioxidant activity of 6-chloro-3-[(4-methylphenoxy) methyl] [1,2,4] triazolo[4,3-b]pyridazine
Sallam, Hamdi Hamid,Mohammed, Yasser Hussien Eissa,Geetha,Al-Ostoot, Fares Hezam,Sridhar,Shaukath, Ara Khanum
, p. 25 - 44 (2021/09/22)
Pyridazine nuclei are essential elements of many natural and synthetic compounds with important biological activities. NMR and IR, as well as studies of mass spectrum, were emplyed to synthesize and characterize the title compound 6-chloro-3-[(4-methylphenoxy) methyl] [1,2,4] triazolo[4,3-b] pyridazine (CMTP). The structure of this compound was confirmed by using single crystal X-ray diffraction technique and it got crystallized in the monoclinic crystal system with the space group P2 1/c. The values of unit cell parameters are: a = 12.0965(7) ?, b = 13.6075(7) ?, c = 7.7686(4) ?, β = 93.942(3)° and Z = 4. Intermolecular hydrogen bonds of two types i.e., C-H…O and C-H…N, were noticed. Hirshfeld surface analysis was employed to account for these interaction bonds. Energy frameworks were carried out to know the dominant interaction energy involved in the molecular packing. DFT calculations were constructed to find the agreement between the theoretical and experimental values. HOMO-LUMO energy levels have been determined; global hardness, global softness, and other quantum chemical parameters have been calculated to reveal the chemical reactivity of the compound. In order to investigate the antioxidant activity of the compound, molecular docking studies were performed.
Design, Synthesis and Biological Evaluation of 5-amino-3-aryl-1-(6′-chloropyridazin-3′-yl)pyrazoles and their Derivatives as Analgesic Agents
Aggarwal, Ranjana,Kaushik, Pawan,Kumar, Ajay,Saini, Deepika
, p. 493 - 502 (2020/09/17)
An efficient and environmental benign solvent-free synthesis of 5-amino-3-aryl-1-(6 '-chloropyridazin-3'-yl)pyrazoles (4a-e) was accomplished by grinding 3-chloro-6-hydrazinopyridazine (2) and β-ketonitriles (3a-e) in the presence of p -toulenesulfonic acid as a catalyst. Subsequently, 6'-chloro group in 4a-e was replaced with cyclic 2° amine derivatives viz. pyrrolidine 5a, piperidine 5b and morpholine 5c to obtain 6a-e, 7a-e, 8a-e respectively. The newly synthesized compounds were characterized by using IR, NMR (1H and 13C), mass spectral studies, elemental analyses. All the synthesized compounds were studied for their docking interaction with target protein 6COX and screened for their in vivo analgesic mode of action against swiss albino mice (animal model) using acetic-acid induced writhing test. Consequently, docking simulations data justifies the potential of synthesized series as an analgesic and very well correlated with in vivo study. Preliminary results revealed that most of the synthesized compounds exhibited moderate to good analgesic activity as compared to reference/standard drug (s) sodium diclofenac and candidates 4d and 7c protrude out as a promising lead for further investigation.
