Final Thoughts on Chemistry for 135034-10-5

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Smectic liquid crystals with ‘de Vries-like’ properties are characterized by a maximum layer contraction of ?1% upon transition from the non-tilted SmA phase to the tilted SmC phase. We show herein that one can systematically increase the ‘de Vries-like’ character of a smectic liquid crystal by tuning the frustration between SmA- and SmC-promoting elements according to established structure-property relationships. The Royal Society of Chemistry 2011.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N3069 – PubChem

 

Final Thoughts on Chemistry for 135034-10-5

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Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors

Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in the biosynthesis of monounsaturated fatty acids from saturated, long-chain fatty acids. Studies with SCD1 knockout mice have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity, with greater whole body insulin sensitivity than wild-type animals. In this work, we have discovered a series of potent, selective, orally bioavailable SCD1 inhibitors based on a known pyridazine carboxamide template. The representative lead inhibitor 28c also demonstrates excellent cellular activity in blocking the conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs in HepG2 cells.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N3067 – PubChem

 

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COMBINATION OF CB2 LIGAND AND PARACETAMOL

Combination of one or more CB2 modulators and paracetamol are useful of treating conditions which are mediated by the activity of CB2 receptors such as an immune disorder, an inflammatory disorder, pain, rheumatoid arthritis, multiple sclerosis, osteoarthritis, and osteoporosis.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N3036 – PubChem

 

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Cognition enhancing derivatives of isoxazole triazoloindane GABA-A alpha 5 receptor subunit ligands

The present invention relates to compounds of formula I: 1 in which R1 is a linear group or a five membered heterocycle optionally fused to a phenyl ring, R2 is a 5-membered heterocycle, R3 is chosen from a range of substituents, m is 0-3 and n is 0 or 1; the compounds are generally inverse agonists at GABA-A receptors containing the alpha 5 subunit and so are useful in methods of enhancing cognition in subjects with diminished cognition in diseases such as Alzheimer”s Disease.

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Reference£º
Pyridazine – Wikipedia,
Pyridazine | C4H4N3032 – PubChem

 

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Design, synthesis and evaluation of MCH receptor 1 antagonists – Part II: Optimization of pyridazines toward reduced phospholipidosis and hERG inhibition

Abstract Despite recent success there remains a high therapeutic need for the development of drugs targeting diseases associated with the metabolic syndrome. As part of our search for safe and effective MCH-R1 antagonists for the treatment of obesity, a series of 3,6-disubstituted pyridazines was evaluated. During optimization several issues of the initial lead structures had to be resolved, such as selectivity over related GPCRs, inhibition of the hERG channel as well as the potential to induce phospholipidosis. Utilizing property-based design, we could demonstrate that all parameters can significantly be improved by consequently increasing the polarity of the compounds. By this strategy, we succeeded in identifying potent and orally available MCH-R1 antagonists with good selectivity over M1 and 5-HT2A and an improved safety profile with respect to hERG inhibition and phospholipidosis.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N3068 – PubChem

 

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PIPERIDINYLAMINO-PYRIDAZINES AND THEIR USE AS FAST DISSOCIATING DOPAMINE 2 RECEPTOR ANTAGONISTS

The present invention relates to 6-(piperidin-4-ylamino)pyridazin-3-carbonitriles of formula (I) that are fast dissociating dopamine 2 receptor antagonists, processes for preparing these compounds, pharmaceutical compositions comprising these compounds as an active ingredient. The compounds find utility as medicines for treating or preventing central nervous system disorders, for example schizophrenia, by exerting an antipsychotic effect without motor side effects.

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Reference£º
Pyridazine – Wikipedia,
Pyridazine | C4H4N3053 – PubChem

 

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Pd-catalyzed chemoselective cross-coupling reaction of triaryl- or triheteroarylbismuth compounds with 3,6-dihalopyridazines

The cross-coupling reactions of 3,6-dihalopyridazines with triaryl- or triheteroarylbismuth compounds were performed under palladium catalysis. The reaction was highly chemoselective, affording functionalized aryl- or heteroarylpyridazinyl chlorides in moderate to good yields. The cross-coupling reactions of 3,6-dihalopyridazines with triaryl- or triheteroarylbismuth compounds were performed under palladium catalysis. The reaction was highly chemoselective, affording functionalized aryl- or heteroarylpyridazinyl chlorides in moderate to good yields. Copyright

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Reference£º
Pyridazine – Wikipedia,
Pyridazine | C4H4N3070 – PubChem

 

Extracurricular laboratory:new discovery of 3-Chloro-6-iodopyridazine

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Mechanism insight and scope of PEPPSI-catalyzed cross-coupling reaction between triarylbismuth and arylbromide

In this paper we report the first cross-coupling reaction of Ar3Bi with Ar’X mediated by Pd-NHC complexes by keeping the ability of Ar3Bi to transfer the three aryl moieties. Investigations were carried out in order to minimize the quantity of the side product Ar-Ar coming from the conversion of Ar3Bi. The results showed that PEPPSI IPr was a good catalyst precursor. Efforts were focussed on the rule of each additive such as PPh3and the base. It was notably found that the presence of PPh3(ratio PEPPSI IPr/PPh3: 1/1) was essential to keep the process efficient. Therefore NHC-Pd-PPh3has been assumed as being the catalytic species. Under the optimized reaction conditions the concomitant formation of the undesired biaryl side product was restricted to its inherent formation consecutive to the reduction of the catalyst precursor to Pd(0). In a last study, the scope and the limitation of the new catalytic methodology were examined and a large range of unsymmetrical biaryl compounds Ar-Ar? bearing various substituents from strongly electron-donating to electron-withdrawing ones have been prepared and fully characterized.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N3063 – PubChem

 

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COMPOUNDS, COMPOSITIONS AND METHODS COMPRISING PYRIDAZINE SULFONAMIDE DERIVATIVES

The present invention relates to compositions and methods for treating a disease in an animal, which disease is responsive to inhibiting of functional cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide by administering to a mammal in need thereof an effective amount of a compound defined herein (including those compounds set forth in Tables 1-3 or encompassed by formula I-III) or compositions thereof, thereby treating the disease. The present invention particularly, relates to a method of treating diarrhea and polycystic kidney disease.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N3055 – PubChem

 

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Heteroatom-substituted analogues of orphan nuclear receptor small heterodimer partner ligand and apoptosis inducer (E)-4-[3-(1-adamantyl)-4- hydroxyphenyl]-3-chlorocinnamic acid

(E)-4-[3′-(1-Adamantyl)-4′-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC) induces the cell cycle arrest and apoptosis of cancer cells. Because its pharmacologic properties-solubility, bioavailability, and toxicity-required improvement for translation, structural modifications were made by introducing nitrogen atoms into the cinnamyl ring and replacing its E-double bond with XCH2 (X = O, N, and S) with the objective of enhancing these properties without impacting apoptosis-inducing activity. Analogues having nitrogen atoms in heterocyclic rings corresponding to the cinnamyl phenyl ring displayed equal or higher biological activities. The pyrimidine and pyridine analogues were more soluble in both phosphate-buffered saline and water. While the 2,5-disubstituted pyridine analogue was the most potent inducer of KG-1 acute myeloid leukemia cell apoptosis, on the basis of apoptotic activity in KG-1 cells and solubility, the 2,5-disubstituted pyrimidine proved to be the more promising candidate for treatment of acute myeloid leukemia.

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Reference£º
Pyridazine – Wikipedia,
Pyridazine | C4H4N3072 – PubChem