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Disclosed are quinoline derivatives as hedgehog pathway inhibitors, especially as SMO inhibitors. Compounds of the present invention can be used in treating diseases relating to hedgehog pathway including cancer.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N1560 – PubChem

 

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A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of a linker that would approximate the spatial arrangement found between the pyrimidine ring and the aryl group at C(7) in ABT-702 was a key element in this modification. A search of potential linkers led to the discovery of an acetylene moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT-702, and adenosine bound to the active site of AK (closed form) in a similar manner with respect to the orientation of the heterocyclic base. Although potent acetylene analogs were discovered based on this assumption, an X-ray crystal structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-ylpyridin-3-ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to adenosine. In addition, this compound bound tightly to a unique open conformation of AK. The structure-activity relationships and unique ligand orientation and protein conformation are discussed.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N1816 – PubChem

 

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The present invention is concerned with novel triazole compounds of formula (I) wherein A, X, Y, Z, R1, R2, and R3 are as described herein, as well as pharmaceutically acceptable salts and esters thereof. The active compounds of present invention have affinity and selectivity for the GABA A alpha5 receptor. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments

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Pyridazine – Wikipedia,
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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 muM, 1.3 muM, 1.4 muM, 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 muM concentration. Finally, an extensive molecular simulation study was performed to investigate the probable interaction with VEGFR-2.

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Pyridazine – Wikipedia,
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A series of 3-amino-6-aryl-pyridazines have been identified as CB2 agonists with high efficacy and selectivity against the CB1 receptor. Details of the investigation of structure-activity relationships (SAR) are disclosed, which led to the identification of pyridazine analogue 35, a compound with high potency in an in vivo model of inflammatory pain.

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Pyridazine – Wikipedia,
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The inventions disclosed herein relate to the discovery of theuse of compounds having the formula shown below and certain subgenera or species thereof, as flavor or tastemodifiers, particularly, savory (?umami?) taste modifiers,savory flavoring agents and savory flavor enhancers in foods,beverages, and other comestible compositions.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N1530 – PubChem

 

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The invention relates to isoxazolo-pyridazine compounds, in particular those of formula I as described above and to a pharmaceutically acceptable salts thereof, having affinity and selectivity for the GABA A alpha5 receptor binding site, their manufacture, pharmaceutical compositions containing them and their use as cognitive enhancers or for the treatment of cognitive disorders like Alzheimer”s disease.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N1228 – PubChem

 

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A series of alkyl (1-3), aryl (6), and benzo-annulated (4,5) heteroaromatic triphenylene analogues with B2N2C2 cores have been synthesized via chelation of pyridazine derivatives using difunctional Lewis acidic diborabiphenyl precursors. In contrast to triphenylene, NICS(1) calculations on 1 suggested high aromaticities for the central (-11.3 ppm) and outer borabenzene rings (-7.7 ppm), along with nonaromatic behavior for the pyridazine ring (-0.7 ppm). Crystal structure analyses supported this analysis. When the a- and c-faces of the pyridazine moiety were free of substitution (1, 3), planar structures resulted, but upon substitution, a twisted B 2N2C2 core was observed due to steric repulsion of neighboring hydrogen atoms (e.g., 5). The increase of steric bulk from H (1) to ?Pr (3) in the planar species was found to result in a dimeric, head-to-tail herringbone packing motif, held together by close intermolecular B…N interactions of 3.39 A. One-electron reduction by Cp*2Co was found to afford the radical anions of 3 and 5, which were characterized by broad, featureless singlets in the EPR spectra; [3] .-[Cp*2Co]- was characterized by X-ray crystallography. While the planar structures (1-4) were observed to possess weak fluorescence (PhiF = 0.02-0.08) with either yellow-orange (ca. 555 nm) or green emission (521 nm), the twisted structures (5, 6) were found to be nonfluorescent.

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Pyridazine – Wikipedia,
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The electronic structures of C4H2Cl2N2 isomers have been studied by HeI photoelectron spectroscopy (PES) combined with the outer valence Green’s function (OVGF) calculations at 6-311++G(d,p) basis sets. The vertical first ionization potentials for 2,6-dichloropyrazine, 2,3-dichloropyrazine, 4,6-dichloropyrimidine and 3,6-dichloropyridazine are determined to be 9.93, 9.89, 10.45 and 10.07 eV, respectively, and the PE spectra were assigned based on molecular orbital analysis and by comparison with related compounds. The effects of chlorine substituent and different positions of nitrogen atoms in these C4H2Cl2N2 isomers have been carefully analyzed by comparing the C4H2Cl2N2 isomers with their matrixes (pyrazine, pyridazine, pyrimidine). The inductive effect of chlorine substituent leads to the stabilization of the nitrogen lone pair orbitals. The resonance effect predominates over the inductive effect, and the consequence is the destabilization of the pi orbitals. Owing to the different positions, the effects of nitrogen atoms are different and lead to the different sequence of pi orbitals.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N1972 – PubChem

 

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3,6-Dihalopyridazines react with the sodium salts of cyanomethylphosphonic acid dialkyl esters or phenylphosphonic acid ethyl ester to yield phosphono- and phosphino-substituted pyridazines.The constitution of one reaction product is proved by X-ray crystal structure analysis.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N1778 – PubChem