More research is needed about 3,6-Dichloropyridazine

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Use of Mc4 Receptor Agonist Compounds

This invention relates to the use of an MC4 receptor agonist compound for the manufacture of a medicament for the treatment of lower urinary tract dysfunction.

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Extracurricular laboratory:new discovery of 141-30-0

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Model Studies toward the Total Synthesis of Thebaine by an Intramolecular Cycloaddition Strategy

Three model compounds required for an approach to thebaine by intramolecular [4+2] cycloaddition were prepared. In the first two cases the anticipated cycloaddition products were obtained under thermal conditions. Thermolysis of the third, more advanced model compound, afforded products resulting from rearrangements and/or elimination. A study of analogous intra- and intermolecular reactions using benzofuran as dienophile and various electron-poor and electron-rich dienes (pyridazines, pyranones, Danishefsky diene) was undertaken.

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Negishi coupling

Over the past 40 years, the Negishi reaction has emerged as a powerful Pd/Ni-catalyzed cross coupling method for the formation of carbon-carbon bonds between an organozinc reagent and organohalide. It has been applied to the construction of a wide array of sp3-sp3, sp3-sp2, and sp2-sp2 carbon bonds. In addition, the scope of this reaction has greatly expanded with the discovery of new organozincate forming methods, innovative catalysts, and novel ligands. Because of these advances, this reaction has emerged as an invaluable tool in organic synthesis. More specifically, the impact in the pharmaceutical industry has been significant, because a plethora of biologically active compounds have been synthesized from milligram to kilo scale utilizing this reaction.

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Synthesis of 4-(N-alkyl-N-heteroaryl)amino-3,4-dihydro-3-hydroxy-2,2- dimethyl-2H-1-benzopyran-6-carbonitrile derivatives via an unusual 1,4- oxygen to nitrogen heteroaryl migration

Various heteroaryls were found to undergo 1,4-oxygen to nitrogen migration (e.g. 4?1) under acidic conditions. This unprecedented migration provides a convenient access to 4-(N-alkyl-N-heteroaryl)amino-3,4-dihydro- 3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile derivatives, which are otherwise difficult to prepare.

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Awesome and Easy Science Experiments about 3,6-Dichloropyridazine

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5b,7b-diaza-3b,9b-diborabenzo[ghi]perylenes

Treatment of a precursor to the chelating Lewis acid 2,2?- diborabiphenyl with 2,6-bisalkynyl-substituted pyridazines, leads to elimination of 2 equiv. of ClSiMe3; subsequent treatment of the mixture with PtCl2 catalyzes the cyclization of observable intermediates to the title 5b,7b-diaza-3b,9b-diborabenzo[ghi]perylene compounds in low isolated yields. The compounds were characterized by NMR and UV-vis spectroscopies, and in one case, by X-ray crystallography. NICS(1) computations indicate that the inner ring is less aromatic than the outer rings.

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Intramolecular Diels-Alder Reactions of 1,2-Diazines: General Indoline Synthesis. Studies on the Preparation of the Central and Right-Hand Segments of CC-1065

An investigation of the intramolecular Diels-Alder reaction of 1,2-diazines and the application of this cycloaddition to a general synthesis of indolines is described.The use of this cycloaddition in a short, regiospecific preparation of the 1,2-dihydro-3H-pyrrolo<3,2-e>indole skeleton, the structural subunit characteristic of the antitumor antibiotic CC-1065, is detailed.

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NEW USE OF THE ADENOSINE ANTAGONIST

The present method for the treatment of pancreatitis, which comprises administering an effective amount of a pyrazolopyridine compound of the following formula: STR1 wherein R 1 is lower alkyl, (substituted) aryl, or a heterocyclic group,

R. sup.2 is a group of the formula STR2 wherein R 4 is protected amino or hydroxy and R 5 is hydrogen or lower alkyl; cyano; a group of the formula–A–R 6, wherein R 6 is an acyl group, and A is (halogenated) lower aliphatic hydrocarbon group; amidated carboxy; an unsaturated heterocyclic group; or (protected) amino; and

< P>R 3 is hydrogen, lower alkyl, lower alkoxy or halogen; or a pharmaceutically acceptable salt thereof, to a human being having pancreatitis or an animal having pancreatitis in need thereof.

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Novel Heterocyclic Compounds as Bromodomain Inhibitors

The present disclosure relates to compounds, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.

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The Absolute Best Science Experiment for 3,6-Dichloropyridazine

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BIARYL MONOBACTAM COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF BACTERIAL INFECTIONS

The present invention relates to biaryl monobactam compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A1, Q, A2, M, W, RX and Rz are as defined herein. The present invention also relates to compositions which comprise a biaryl monobactam compound of the invention or a pharmaceutically acceptable salt therof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of a second beta-lactam antibiotic.

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Discovery of 2-(3,4-dialkoxyphenyl)-2-(substituted pyridazin-3-yl)acetonitriles as phosphodiesterase 4 inhibitors with anti-neuroinflammation potential based on three-dimensional quantitative structure?activity relationship study

Phosphodiesterase 4 (PDE4) inhibitors with potential activities for CNS disorders provide a new therapeutic strategy for depression. To discover PDE4 inhibitors with anti-neuroinflammation activities, reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) models on our previous reported catecholic PDE4 inhibitors was built with a statistically significant cross-validated coefficient (q2), conventional coefficient (r2), and good predictive capabilities based on the molecular docking results, using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) methods. Based on the analysis of CoMFA and CoMSIA contour maps, a series of 2-(3,4-dialkoxyphenyl)-2-(substituted pyridazin-3-yl) acetonitriles 16a?i was designed and synthesized. Among these compounds, compound 16a exhibited good inhibitory activities toward PDE4B1 and PDE4D7 with mid-nanomolar IC50 values and potential anti-neuroinflammation activity in BV-2 cells. Docking simulation of compound 16a in the PDE4 catalytic domain activity pocket revealed that compound 16a maybe assumed a ?V-shaped? conformation, extending the side chain to S-pocket.

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