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The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of GPR119.

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Employing the multicarboxylate and N-donor mixed ligands to react with Zn(NO3)2·6H2O affords a new 3D compound [Zn3(HBPTC)2(bmp)2(H2O)2]·2H2O (1) (H4BPTC = biphenyl-3,3?,4,4?-tetracarboxylic acid, bmp = 3,6-bis(imidazol-1-yl)pyridazine). Structural analyses show that compound 1 possesses a (4,4)-connected neutral framework bearing rare NbO-x-d subnets, and it represents the first replica of the theoretically predicted NbO-x-d/Im-3m?Imm2 topology net. Moreover, compound 1 can demonstrate the interesting reversible structural transformation property induced by water molecules. Additionally, thermal stability and luminescence properties of 1 were investigated.

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A novel process is described for preparing substituted pyridazines, where a less substituted pyridazine is reacted with a carboxylic acid in the presence of a silver ion as catalyst, using peroxydisulfate ion. The reaction is run at a temperature from about 40 to 80 C. in an aqueous solvent system and mineral acid. The substituted pyridazines are useful as intermediates to herbicidal and fungicidal compounds.

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La condensation du reactif de Grignard du bromo-2-thiophene avec les derives bihalogenes, tels que le dichloro-1,2-ethene (Z), la dichloro-2,4-pyrimidine et la dichloro-3,6-pyridazine, en presence de catalyseur a base de metal de transition permet d’obtenir, en une seule etape, des derives polycycliques, comportant deux noyaux thiophenes.

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Reaction of 2-benzyl-5-halopyridazin-3(2H)-ones (3) with Grignard reagents followed by quenching with electrophiles unexpectedly yielded 4,5-disubstituted pyridazin-3(2H)-ones instead of 5-substituted pyridazin-3(2H)-ones. These reactions represent the first examples of cine substitution in which the anionic sigmaH-adduct is quenched by electrophiles (other than a proton) before elimination takes place. Insight into the reaction mechanism led to the direct transformation of 2-benzylpyridazin-3(2H)-one (7) and 2-benzyl-6-chloropyridazin-3(2H)-one (9) into the corresponding C-4 alkyl and aryl derivatives (when Br2 was used as the electrophile).

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The magnetic and decay properties of the short-lived triplet ( T1) states of pyridazine and 3, 6-dichloropyridazine ( DCP ) were studied by means of time-resolved EPR with laser excitation.The zfs of DCP in the p-dibromobenzene ( DBB ) host are X = 0.094 cm-1, – Y = – 0.164 cm-1, and Z = 0.070 cm-1, and the nitrogen hfcc are Ax = 27 G, Ay =18 G, and Az = 25 G, which confirms the n?* character of the T1 state.Similar zfs were obtained for DCP and pyridazine in other environments.The sublevel decay rate constants and the relative populating rates were determined from the analysis of the transient EPR signals measured at 3.0 K where the effect of the spin lattice relaxation can be neglected.It was found in both systems that ky is much greater than kx , kz as predicted by a simple group theoretical consideration. ky of DCP and pyridazine were determined to be on the order of 106 s-1, being larger than that of pyrimidine by a factor of ca. 104.The reasons for the large ky are discussed, particularly, in terms of the distorted potential of the T1 state.

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The invention relates to a series of compounds useful for inhibiting histone deacetylase (HDAC) enzymatic activity. The invention also provides a method for inhibiting histone descetylase in a cell using said compounds as well as a method for treating cell proliferative diseases and conditions using said HDAC inhibitors. Further, the invention provides pharmaceutical compositions comprising the HDAC inhibiting compounds and a pharmaceutically acceptable carrier.

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This invention relates to a novel phenyl triazole derivative, pharmaceutical compositions containing this compound, and methods of treatment therewith. The compound of the invention is in particular considered useful for the treatment of central nervous system diseases and disorders which are responsive to modulation of GABAA receptors containing the a5 subunit.

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The present invention relates to difluoromethyl-phenyl triazoles of general formula (I) which are modulators of GABAA receptors containing the alpha5 subunit, useful in treating central nervous system diseases and other diseases. In addition, the invention relates to processes for preparing pharmaceutical compositions as well as processes for manufacture the compounds according to the invention.

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A novel series of 1,2,4-thiadiazole compounds was discovered as selective S1P1 agonists. The extensive structure-activity relationship studies for these analogues were reported. Among them, 17g was identified to show high in vitro potency with reasonable free unbound fraction in plasma (Fu > 0.5%), good brain penetration (BBR > 0.5), and desirable pharmacokinetic properties in mouse and rat. Oral administration of 1 mg/kg 17g resulted in significant peripheral lymphocytes reduction at 4 h after dose and rapid lymphocytes recovery at 24 h. 17g showed a transient lymphopenia profile in the repeated dose study in mouse. In addition, 17g also demonstrated efficacy comparable to that of FTY720 (1) in the mouse EAE model of MS.

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