- Structurally diverse copper(ii) complexes with pyridazine-integrated with pyrazine-Schiff base ligand featuring an easily lost proton in the hydrazone backbone
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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.
- Cao, Jing,Liu, Jia-Cheng,Deng, Wen-Ting,Jin, Neng-Zhi
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- A photochromic diarylethene-functionalized fluorescent probe for Cd2+ and Zn2+ detections
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A novel bifunctional chemosensor 1O constructed with diarylethene and pyridazine unit has been designed and synthesized with excellent photochromic properties upon UV/Vis radiation. The chemosensor 1O shows prominent selectivity and high sensitivity for Cd2+ and Zn2+ by obvious fluorescent enhancement with a low detection limit in water-acetonitrile solution (v(water):v(acetonitrile) = 1:9). The chemosensor 1O could be utilized as a fluorescent sensor for Cd2+ with a limit of detection (LOD) of 2.3 × 10?6 M. With the presence of Zn2+, the fluorescence of the generated zinc complex enhances remarkably and the limit of detection (LOD) for Zn2+ is calculated to be 1.1 × 10?5 M by Job's plot titrations. A logic circuit of this chemosensor 1O has been constructed with the input signals of UV and visible light, Cd2+ (or Zn2+) and EDTA and the output signal of the emission intensity. In addition, the concentrations of Cd2+ or Zn2+ in real water are detected quickly and conveniently by this chemosensor.
- Peng, Shanxi,Lv, Junfei,Liu, Gang,Fan, Congbin,Pu, Shouzhi
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- Pyridazine-versus pyridine-based tridentate ligands in first-row transition metal complexes
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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.
- Gruenwald, Katrin R.,Volpe, Manuel,Cias, Pawel,Gescheidt, Georg,Moesch-Zanetti, Nadia C.
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- Solubility and transfer processes of some hydrazones in biologically relevant solvents
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Solubility values of 20 hydrazones in water, 1-octanol and hexane were determined by the isothermal saturation method. Thermophysical characteristics of fusion processes (melting points and fusion enthalpies) of the selected substances were measured by DS
- Perlovich, German L.,Kazachenko, Vladimir P.,Strakhova, Nadezda N.,Schaper, Klaus-J.,Raevsky, Oleg A.
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- Machine-assisted synthesis of modulators of the histone reader BRD9 using flow methods of chemistry and frontal affinity chromatography
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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
- 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.
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- New pyridazine-based binuclear nickel(II), copper(II) and zinc(II) complexes as prospective anticancer agents
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A new class of pyridazine-based binuclear nickel(II), copper(II) and zinc(II) complexes of the type [M2(L1-3)2](NO3)2 (1-9) with tridentate Schiff base ligands 3-chloro-6-(salicylidenehydrazinyl)pyrid
- Rafi, Ummer Muhammed,Mahendiran, Dharmasivam,Haleel, Azees Khan,Nankar, Rakesh Pandeet,Doble, Mukesh,Rahiman, Aziz Kalilur
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- Synthesis and identification of novel pyridazinylpyrazolone based diazo compounds as inhibitors of human islet amyloid polypeptide aggregation
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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.
- 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
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- Design and Synthesis of Novel 3-(2-Aminopyridin-3-yl)-1,2,4-Triazolo[4,3-b]Pyridazine Derivatives as a Reversible Bruton's Tyrosine Kinase Inhibitors
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Bruton's tyrosine kinase, a non-receptor TEC family kinase, plays key role in B cell differentiation, proliferation, and survival. B cell receptor regulates the B cell's fate and cytokine release of B-lineage lymphoid leukemia cells which are deeply related with the pathogenesis of B-cell lineage of lymphoma and leukemia and autoimmune diseases. Thus, BTK protein regulation emerged as a promising therapeutic target for both various cancers and autoimmune diseases. Herein, we report the discovery of aminopyridin-1,2,4-triazolopyridazine derivatives as a reversible BTK inhibitor, and in vitro enzyme assay and cell based assay result were reported.
- Park, Chi Hoon,Kim, Dukwoon,Jung, Hyeonseok,Jeon, Jeong Hee,Achary, Raghavendra,Lee, Joo-Youn,Kim, Pilho,Jung, Heejung,Hwang, Jong Yeon,Ryu, Do Hyun,Du Ha, Jae,Cho, Sung Yun
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- Multinuclear magnetic resonance study of the structure and tautomerism of azide and iminophosphorane derivatives of chloropyridazines
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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
- Cmoch, Piotr
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- INHIBITORS OF LIN28 AND METHODS OF USE THEREOF
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The present disclosure relates to compounds of formula (I) and compositions comprising the same. The disclosure further relates to methods of treating cancers.
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Page/Page column 52-53; 86
(2021/06/26)
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- 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
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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.
- Sallam, Hamdi Hamid,Mohammed, Yasser Hussien Eissa,Geetha,Al-Ostoot, Fares Hezam,Sridhar,Shaukath, Ara Khanum
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- Synthesis, crystal structure characterization, DFT calculations, Hirshfeld surface analysis and 3D energy frameworks of triazole pyridazine derivatives: Theoretical and experimental studies
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Recently, pyridazine derivatives have shown considerable biological properties such as anti-tumor and anti-inflammatory activity. The studied compounds 6-chloro-3-[(4-methylphenoxy)methyl][1,2,4] triazolo[4,3-b]pyridazine (8a) and 6-chloro-3-[(4-fluorophenoxy)methyl][1,2,4] triazolo[4,3-b]pyridazine (8b) have been synthesized and characterized by NMR, IR and mass spectral studies, and finally, the structures were confirmed by single crystal X-ray diffraction technique. The compounds 8a and 8b have crystallized in the same crystal system with different space groups. Density functional theory calculations were performed to compare the theoretical and experimental results obtained from XRD. Further, DFT calculations were employed to determine HOMO-LUMO energy levels, energy gap, softness, hardness, and other quantum chemical parameters of the compounds 8a and 8b. Hirshfeld surface analysis was carried out to distinguish the different intermolecular hydrogen bonds. Energy frameworks for the compounds were constructed through different intermolecular interaction energies to know the dominant interaction energy involved in the molecular packing strength.
- Al-Ostoot, Fares Hezam,Khanum, Shaukath Ara,M. A., Sridhar,Mohammed, Yasser Hussien Issa,Sallam, Hamdi Hamid
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- Design, Synthesis and Biological Evaluation of 5-amino-3-aryl-1-(6′-chloropyridazin-3′-yl)pyrazoles and their Derivatives as Analgesic Agents
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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.
- Aggarwal, Ranjana,Kaushik, Pawan,Kumar, Ajay,Saini, Deepika
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p. 493 - 502
(2020/09/17)
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- Synthesis and bioevaluation of 6-chloropyridazin-3-yl hydrazones and 6-chloro-3-substituted-[1,2,4]triazolo[4,3-b]pyridazines as cytotoxic agents
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An efficient synthesis of a series of 6-chloro-3-substituted-[1,2,4]triazolo[4,3-b]pyridazines is described via intramolecular oxidative cyclization of various 6-chloropyridazin-3-yl hydrazones with iodobenzene diacetate. The structures of the newly synth
- Mamta,Aggarwal, Ranjana,Sadana, Rachna,Ilag, Jeziel,Sumran, Garima
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p. 288 - 295
(2019/02/12)
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- 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
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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.
- Jaballah, Maiy Y.,Serya, Rabah A. T.,Saad, Nasser,Khojah, Sohair M.,Ahmed, Marawan,Barakat, Khaled,Abouzid, Khaled A. M.
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p. 1573 - 1589
(2019/09/12)
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- Towards dual inhibitors of the MET kinase and WNT signaling pathway; Design, synthesis and biological evaluation
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Both the kinase MET and the WNT signaling pathway are attractive targets in cancer therapy, and synergistic effects have previously been observed in animal models upon simultaneous inhibition. A strategy towards a designed multiple ligand of MET and WNT signaling is pursued based on the two hetero biaryl systems present in both the MET inhibitor tepotinib and WNT signaling inhibitor TC-E 5001. Initial screening was conducted to find the most suitable ring systems for further optimization, whereas a second screen explored modifications towards pyridazinones and triazolo pyridazines. Up to 54% reduction of WNT signaling activity at 10 μM concentration was achieved, however, only low affinities towards MET were observed. Overall, the thiophene substituted pyridazinone 40 was the best dual MET and WNT signaling inhibitor, with a 17% and 19% reduction of activity, respectively. Although further optimizations are needed to achieve more potent dual inhibitors, the strategy presented herein can be valuable towards the development of a dual inhibitor of MET and WNT signaling.
- Lien, Vegard Torp,Kristiansen, Margrethe Konstanse,Pettersen, Solveig,Haugen, Mads Haugland,Olberg, Dag Erlend,Waaler, Jo,Klaveness, Jo
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p. 37092 - 37100
(2019/11/25)
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- Triazolo-pyridazine derivatives, preparation method thereof, and pharmaceutical composition for use in preventing or treating Bruton's tyrosine kinase activity related diseases containing the same as an active ingredient
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The present invention relates to a triazolopyridazine derivative, a production method thereof, and a pharmaceutical composition for preventing or treating diseases associated with activation of Brutonandprime;s tyrosine kinase (BTK) containing the same as an active ingredient. According to the present invention, the triazolopyridazine derivative excellently inhibits BTK, and thus can be useful for preventing or treating diseases associated with activation of BTK, especially cancer or autoimmune diseases.COPYRIGHT KIPO 2018
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Paragraph 0221; 0222; 0223; 0224
(2018/10/16)
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- Method for synthesizing 3-chloro-6-hydrazinopyridazine
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The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing 3-chloro-6-hydrazinopyridazine. The method for synthesizing 3-chloro-6-hydrazinopyridazine comprises the following steps: taking 3,6-dichloropyridazine and hydrazine hydrate as raw materials, carrying out a reaction at an appropriate temperature for several hours under the action of an appropriate solvent, and generating 3-chloro-6-hydrazinopyridazine; purifying, thereby obtaining the pure 3-chloro-6-hydrazinopyridazine. The method for synthesizing 3-chloro-6-hydrazinopyridazine disclosed by the invention has the beneficial effects of being highly available in reaction raw materials, reasonable in price, mild in reaction conditions, easy to operate and control and simple in after-treatment, and the product is stable in quality and high in purity.
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Paragraph 0015
(2017/07/04)
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- The anti-invasive role of novel synthesized pyridazine hydrazide appended phenoxy acetic acid against neoplastic development targeting matrix metallo proteases
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Neoplastic metastasis is a major process where tumor cells migrate from the primary tumor and colonize at other parts of our body to form secondary tumor. Cancer incidences are rising and novel anti-neoplastic compounds with new mechanism of actions are essential for preventing cancer related deaths. In the current examination, a novel series of pyridazine analogues 6a-l was synthesized and evaluated against metastatic neoplastic cells. Experimental data postulated compound 6j has potential cytotoxic efficacy with prolonged activity against various cancer cells, including A549, HepG2, A498, CaSki and SiHa cells. Moreover, compound 6j arrests the A549 migration and invasions markedly by counteracting matrix metalloproteinase (MMP)-2 and MMP-9 expressions. Also, compound 6j proved its potentiality against Dalton's solid lymphoma progression in-vivo by abridging MVD and MMP expressions. Compound 6j interacts with MMP-2 and MMP-9 by H- bond in-silico, thereby down regulates the MMPs action in tumourigenesis. Altogether, we concluded that compound 6j down regulates MMP-2 and MMP-9 and thereby impairs metastatic cancer cell migration and invasions which can be translated into a potent anti-neoplastic agent.
- Eissa Mohammed, Yasser Hussein,Thirusangu, Prabhu,Zabiulla,Vigneshwaran,B.T, Prabhakar,Khanum, Shaukath Ara
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p. 375 - 386
(2017/09/02)
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- Synthesis of Some Novel 2,6-Disubstituted Pyridazin-3(2H)-one Derivatives as Analgesic, Anti-Inflammatory, and Non-Ulcerogenic Agents
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Some novel 2,6-disubstituted pyridazine-3(2H)-one derivatives were synthesized and evaluated for in vitro cyclooxygenase-2 (COX-2) inhibitory efficacy. Compounds 2-{[3-(2-methylphenoxy)-6-oxopyridazin-1(6H)-yl]methyl}-1H-isoindole-1,3(2H)-dione (5a), 2-pr
- Ibrahim, Tamer H.,Loksha, Yasser M.,Elshihawy, Hosam A.,Khodeer, Dina M.,Said, Mohamed M.
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- Synthesis, biological activities and molecular docking simulation of hydrazone scaffolds of carvacrol, thymol and eugenol
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In present work, we report the synthesis of 12 new hydrazones and sulfonyl hydrazones linkage containing carvacrol, thymol and eugenol derivatives by simple condensation reactions. Synthesized derivatives have been characterized by 1H NMR, 13C NMR, LC–MS, and X-ray single crystallography techniques, and these derivatives were screened for anticancer testing by using sulforhodamine B assay and anti-oxidant testing by using DPPH assay. Docking studies of all the derivatives against the active site of human heme oxygenase-1 indicated that interaction with the maximum site of the amino acid residue of human heme oxygenase-1 was crucial for anti-oxidant activity. The results show that all derivatives possess interesting biological activities.
- Rajput, Jamatsing D.,Bagul, Suresh D.,Bendre, Ratnamala S.
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p. 6601 - 6616
(2017/10/05)
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- Synthesis of new derivatives of pyridazino[6,1-c]pyrimido[5,4-e][1,2,4]triazine; a novel heterocyclic system
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Several derivatives of the novel pyridazino[6,1-c]pyrimido[5,4-e][1,2,4]triazine ring system have been synthesised through heterocyclisation of 5-bromo-2,4-dichloro-6-methylpyrimidine with 3-chloro-6-hydrazinylpyridazine followed by treatment with secondary amines in boiling ethanol.
- Akaberi, Toktam,Shiri, Ali,Sheikhi-Mohammareh, Seddigheh
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- TRIAZOLOPYRIDAZINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
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A series of substituted [1,2,4]triazolo[4,3-b]pyridazine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflamma
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(2015/06/25)
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- BROMODOMAIN INHIBITORS AND USES THEREOF
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The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions i
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Paragraph 0361; 0362
(2014/10/16)
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- Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a [1,2,4]triazolo[4,3-b]pyridazine scaffold
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Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD). The most common mutant, G2019S, increases kinase activity, thus LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein disclose the str
- Galatsis, Paul,Henderson, Jaclyn L.,Kormos, Bethany L.,Han, Seungil,Kurumbail, Ravi G.,Wager, Travis T.,Verhoest, Patrick R.,Noell, G. Stephen,Chen, Yi,Needle, Elie,Berger, Zdenek,Steyn, Stefanus J.,Houle, Christopher,Hirst, Warren D.
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p. 4132 - 4140
(2014/09/17)
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- SUBSTITUTED BENZOFURAN COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
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The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.
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(2013/03/26)
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- Synthesis, antibacterial and antioxidant properties of pyrazolylpyridazines
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A number of 6-chloro-3-(pyrazol-1′-yl) pyridazines were prepared from 3,6-dichloropyridazine via either reaction with hydrazine followed I by reaction with appropriate reagents to develop the pyrazole or through a nucleophilic reaction with a pyrazole. So
- Ather, Abdul Qayuum,Chaudhry, Faryal,Khan, Muhammad Naeem,Bueno, Eliana Aparecida Silicz,Khan, Misbahul Ain,Aslam, Noreen,Khan, Khalid M.,Athar, Muhammad Makshoof,Munawar, Munawar Ali,Ashraf, Muhammad,Ejaz, Syeda Abida
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p. 7743 - 7748
(2013/09/23)
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- DERIVATIVES OF 6-SUBSTITUTED TRIAZOLOPYRIDAZINES AS REV-ERB AGONISTS
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The present invention provides novel 6-substituted [1,2,4]triazolo[4,3-b]pyridazines that are agonists of Rev-Erb. These compounds, and pharmaceutical compositions comprising the same, are suitable means for treating any disease wherein the activation of Rev-Erb has therapeutic effects, for instance in inflammatory and circadian rhythm-related disorders or cardiometabolic diseases.
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(2013/04/13)
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- Microwave-enhanced efficient synthesis of some polyfunctional pyridazines
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Microwave-enhanced highly efficient protocol for the synthesis of polyfunctional pyridazines beginning from 3,6-dichloropyridazine in environmentally benign ionic liquids have been developed. The products obtained were 3-amino-6-chloropyridazine, 3,6-diaminopyridazine, and 3-chloro-6- methoxypyridazine. These derivatives were then be converted to a variety of polyfunctional pyridazine derivatives. The ionic liquids used were 1-n-butyl-3-methylimidazolium hydroxide/tetrafluoroborate/hexafluorophosphate and 1,3-di-n-butylimidazolium hydroxide. This powerful strategy is less time-consuming green methodology. The ionic liquid employed may be recovered and recycled.
- Kumar Jangid,Yadav,Yadav
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p. 1165 - 1173
(2013/10/21)
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- HETEROCYCLIC HYDRAZONE COMPOUNDS AND THEIR USES TO TREAT CANCER AND INFLAMMATION
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The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).
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Page/Page column 62-63
(2011/02/24)
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- HETEROCYCLIC OXIME COMPOUNDS
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The invention relates to compounds of formula (I) and salts thereof wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).
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Page/Page column 67
(2011/04/13)
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- Synthesis and antiproliferative activity of 2-(([1,2,4]triazolo[4,3-b]- pyridazin-6-yloxy)methyl)-2,4-dimethyl-3,4-dihydro-2Hbenzo[b][1,4]oxazine derivatives
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A small library of [1,2,4]triazolo[4,3-b]pyridazin-6-yloxy derivatives 14-17 of N-benzyl-N-(2-((4-amidinophenoxy)methyl)-2,4-dimethyl-3,4-dihydro-2H- benzo[b][1,4]oxazin-7-yl)-oxalic acid monoamides 1 was prepared by replacement of benzamidine with a [1,2
- Ilic, Milos,Ilas, Janez,Liekens, Sandra,Matyus, Peter,Kikelj, Danijel
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scheme or table
p. 298 - 311
(2011/12/15)
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- Asymmetric allylation, crotylation, and cinnamylation of N-heteroaryl hydrazones
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(Chemical Equation Presented) A new class of N-heteroaryl hydrazones has been developed as an alternative to N-acylhydrazones and 2-amlnophenol-derlved lmlnes In asymmetric allylatlon, crotylatlon, and clnnamylatlon reactions with chlral allylchlorosllanes. The hydrazones are readily and Inexpensively prepared, perform well In the allylatlon chemistry, and more Importantly, the product hydrazldes may be smoothly reduced by Pd(OH)2catalyzed hydrogenation to reveal the corresponding amine products.
- Feske, Miriam Inbar,Santanilla, Alexander Buitrago,Leighton, James L.
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supporting information; experimental part
p. 688 - 691
(2010/04/02)
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- Synthesis, fungicidal and antibacterial activity of new pyridazine derivatives
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Compounds 1-3 were obtained in the reaction of 3,6-dichloro-pyridazines with phenylacetonitriles in the biphasic system - DMSO/50% NaOH. The chlorine atom was replaced with cycloalkylamino (4-13) and hydrazinyl (23, 24) moiety. These last compounds were condensed with aldehydes (25-34). Pyridazynylphenylacetonitriles were converted into amides 14-18 and thioamides 19-22. In compounds 2, 3 the chlorine atom was replaced with thiophenyl (37, 38) and in compound 1 with thioethyl and thiophenyl (35, 36) functional groups. In the reactions of compounds 1, 2 with ammonium polysulfide thioamides with thiol group (39, 40) and chlorine atom (41, 42) were obtained. Compounds 1-17, 19-43 were screened for antibacterial and fungicidal activities.
- Foks, Henryk,Wisterowicz, Krystyna,Miszke, Agnieszka,Brozewicz, Kamil,Wisniewska, Katarzyna,Dabrowska-Szponar, Maria
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experimental part
p. 961 - 975
(2009/09/30)
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- INHIBITORS OF C-MET AND USES THEREOF
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The present invention provides compounds useful as inhibitors of c-Met tyrosine kinase. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment o
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Page/Page column 81; Figure 5
(2008/06/13)
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- Process for preparing alkoxyalkylidenehydrazinopyridazine derivatives
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A novel process for preparing alkoxyalkylidenehydrazinopyridazine derivatives which comprises reducing a novel alkoxytriphenylmethylazopyridazine derivative, removing the triphenylmethyl group and reacting with an aldehyde or ketone derivative. A specific
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- Process for preparing alkoxyalkyl-idenehydrazinopyridazine derivatives
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A process for preparing a compound of the formula (4): is described wherein R3 and R4 are both hydrogen or together are =CR1R2, where R1 is hydrogen or C1-3alkyl and R2 is C1-3alkyl, carboxy or phenyl,which comprises reduc
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- Synthesis and Structure-Activity Relationships of Series of Aminopyridazine Derivatives of γ-Aminobutyric Acid Acting as Selective GABA-A Antagonists
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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.
- Wermuth, Camille-Georges,Bourguignon, Jean-Jacques,Schlewer, Gilbert,Gies, Jean-Pierre,Schoenfelder, Angele,et al.
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p. 239 - 249
(2007/10/02)
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- Studies in the field of pyridazine compounds, III (1). Hypotensive 3-(1-pyrazolyl) pyridazine derivatives
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Substituted 3-(1-pyrazolyl)pyridazines were synthesized and their hypotensive activity was evaluated on anaesthetized normotensive cats and awake spontaneously hypertensive rats. Several relations were found between structure and hypotensive activity of the compounds. Some of the active compounds proved to be useful for detailed investigations. Most of the active compounds exerted an influence on prostaglandin metabolism.
- Szilagyi,Kasztreiner,Tardos,et al.
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p. 439 - 445
(2007/10/05)
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