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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.

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Reference:
Pyridazine – Wikipedia,
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A series of 3,6-bis(4-triazolyl)pyridazines equipped with terminal phenyl substituents with varying degree of fluorination were synthesized by using the facile copper-catalyzed azide?alkyne cycloaddition and their structures were thoroughly investigated in the gas phase, in solution, and in the solid state by employing DFT calculations, NMR spectroscopy, and single-crystal X-ray diffraction, respectively. On the molecular level, their structure is governed by the strong preference of the triazole-pyridazine linkages for the anti-conformation. The supramolecular organization of the molecules in the crystalline solid is controlled by pi-stacking, C?H???pi as well as C?F???H interactions. The latter can conveniently be tuned by the number and position of fluorine substituents in the terminal phenyl units, giving rise to either herringbone-like, 1D or 2D lamellar packing. Electrochemistry and optical spectroscopy of all compounds suggest that they might find use as electron-transporting/hole-blocking materials in organic electronics.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N1622 – PubChem

 

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The syntheses of 23 new chelating ligands are described.Most of these ligands are derived from the chiral pyrazole (1) which has been linked to a variety of heterocycles, namely pyridine, pyrimidine, pyridazine, isoxazole, benzimidazole, thiophen and furan.In certain cases the parent achiral analogues have also benn prepared.Preliminary studies of the coordination chemistry of these ligands with selected transition metals have been carried out.The X-ray crystal structures of palladium complexes of isoxazole- and thiophen-containing ligands have also been determined.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N1953 – PubChem

 

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Disclosed herein are substituted 2-azaspiro[3.3]heptane compounds, which may be useful as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating disorders using the compounds and compositions.

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Pyridazine – Wikipedia,
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A new family of bridged cyclometallating ligands is reported, which incorporate two terdentate N?C?N-coordinating binding sites linked via pyrazine, pyrimidine or pyridazine units. Dinuclear Ir(iii) complexes of one ligand have been prepared and crystallographically characterised; they display intense red phosphorescence. the Partner Organisations 2014.

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Pyridazine – Wikipedia,
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Tetrahydroquinoline compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.

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The synthesis, structural, electrochemical, optical, and electronic structure properties of a new azinethiophene semiconductor family are reported and compared to those of analogous oligothiophenes. The new molecules are: 5,5?-bis(6-(thien-2-yl)pyrimid-4-yl)-2,2?-dithiophene (1), 5,5?-bis(6-(5-hexylthien-2-yl)pyrimid-4-yl)-2,2?-dithiophene (3), and 5,5?-bis(6-(thien-2-yl)pyridazin-3-yl))-2,2?-dithiophene (2). Electrochemical experiments demonstrate that introduction of electron-poor heteroaromatic rings into the oligothiophene core significantly enhances electron affinity. Thin-film transistors were fabricated with these materials and evaluated both in vacuum and in air. We find that although diazine substitution is important in tuning oligothiophene orbital energetics, these oligomers are p-channel semiconductors and the field-effect transistor (FET) charge transport properties are remarkably similar to these of unsubstituted oligothiophenes. The combined computational-experimental analysis of the molecular and thin film properties indicates that these diazine-containing oligothiophenes essentially behave as pi-extended bithiophenes. Interestingly, despite strong intermolecular interactions, high solid-state fluorescence efficiencies are observed for these new derivatives. Such emission characteristics suggest that these materials behave as more extended pi systems, which should be advantageous in light-emitting transistors.

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Therapeutic compounds are disclosed having the general formula (I) that are useful for the treatment of metabolic disorders, including type II diabetes. The compounds have activity as agonists of GPR119. Compounds having the stereochemistry of formula (la) may also demonstrate DPP-IV inhibitory activity

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An efficient two-step synthesis of 3,6-diaminopyridazine from 3,6-dichloropyridazine is reported. In this synthetic procedure, 4-methoxybenzylamine was used as a nitrogen source to substitute the chloro groups of 3,6-dichloropyridazine to form N,N’-bis-(4-methoxybenzyl)-pyridazine- 3,6-diamine. The 4-methoxybenzyl groups were then removed by treatment with hydrochloric acid to provide the target 3,6-diaminopyridazine with an overall yield of 78%. Copyright Taylor & Francis Group, LLC.

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Using molecular modeling and rationally designed structural modifications, the multi-target structure?activity relationship for a series of ranitidine analogs has been investigated. Incorporation of a variety of isosteric groups indicated that appropriate aromatic moieties provide optimal interactions with the hydrophobic and pi?pi interactions with the peripheral anionic site of the AChE active site. The SAR of a series of cyclic imides demonstrated that AChE inhibition is increased by additional aromatic rings, where 1,8-naphthalimide derivatives were the most potent analogs and other key determinants were revealed. In addition to improving AChE activity and chemical stability, structural modifications allowed determination of binding affinities and selectivities for M1?M4 receptors and butyrylcholinesterase (BuChE). These results as a whole indicate that the 4-nitropyridazine moiety of the JWS-USC-75IX parent ranitidine compound (JWS) can be replaced with other chemotypes while retaining effective AChE inhibition. These studies allowed investigation into multitargeted binding to key receptors and warrant further investigation into 1,8-naphthalimide ranitidine derivatives for the treatment of Alzheimer’s disease.

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Pyridazine – Wikipedia,
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