The Absolute Best Science Experiment for 3,6-Dichloropyridazine

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Deprotonative metalation of substituted benzenes and heteroaromatics using amino/alkyl mixed lithium-zinc combinations

Different homoleptic and heteroleptic lithium-zinc combinations were prepared, and structural elements obtained on the basis of NMR spectroscopic experiments and DFT calculations. In light of their ability to metalate anisole, pathways were proposed to justify the synergy observed for some mixtures. The best basic mixtures were obtained either by combining ZnCl 2¡¤TMEDA (TMEDA = N,N,N’,N’tetramethylethylenediamine) with [Li(tmp)] (tmp = 2,2,6,6-tetramethylpiperidino; 3 equiv) or by replacing one of the tmp in the precedent mixture with an alkyl group. The reactivity of the aromatic lithium zincates supposedly formed was next studied, and proved to be substrate-, base-, and electrophile-dependent. The aromatic lithium zincates were finally involved in palladium-catalyzed cross-coupling reactions with aromatic chlorides and bromides.

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Intramolecular fixation of t-butyl groups in thiolactim ethers influencing molecular conformation and the packing behavior

Derived from the result of a previous crystallographic study regarding an ethynylene bridged bispyrimidine, the presence of two intramolecular C-H…N hydrogen bonding contacts being responsible for a fixation of the terminal t-butylthio units to the azine nitrogens was noticed. Acting as stimulus, a series of different pyridine and pyridazine derivatives also featuring this unusual functionality has been synthesized and structurally studied. In order to support the investigations concerning this particular bonding pattern performed via X-ray structure analysis, calculations based on the density functional theory were carried out. It was found that the formation of the intramolecular hydrogen bonding motif has not only impact on the molecular stability but in some cases also predictably influences the reactivity and the packing behavior of the different heterocycles.

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Novel diarylpyridinones, diarylpyridazinones and diarylphthalazinones as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs)

In this Letter, we report on diarylpyridinone, diarylpyridazinone and diarylphthalazinone analogs as potential inhibitors of HIV-1 nonnucleoside reverse transcriptase (NNRTIs). The most promising compounds in these series are three diarylpyridazinones 25a, 25l and 25n which demonstrated submicromolar activity against wild-type HIV-1 and moderate activity against the single mutant strain Ba-L V106A.

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Certain herbicidal N-(meta-(6-chloro-3-pyridazinyloxy)phenyl)trifluoromethanesulfonamides

Certain N-(meta-(6-chloro-3-pyridazinyloxy)phenyl)trifluoromethanesulfonamides and their use as herbicides.

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MELANOCORTIN RECEPTOR AGONISTS

The present invention relates to a compound having a good agonistic activity to melanocortin receptor, or pharmaceutically acceptable salt or isomer thereof, and an agonistic composition for melanocortin receptor comprising the same as an active ingredient

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Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones

Cycloaddition of pyridine N-imine with 6-alkyl-4-oxohex-5-ynoates followed by condensation with hydrazine provides concise access to pharmacologically active 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazinones. For the first time alkynyl heterocycles are also shown to be effective dipolarophiles for pyridine N-imine, and analogous compounds can be accessed directly in modest yields through the reaction of 6-(alkyn-1-yl)pyridazin-3-one derivatives. The Royal Society of Chemistry 2008.

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NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS

The present invention discloses compounds according to Formula I: (Formula I) Wherein R1, L1, R2, L2, R3, Cy, and the subscript n are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of allergic diseases, inflammatory diseases, metabolic diseases, autoinflammatory diseases, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IFNalpha, IL12 and/or IL23 by administering the compound of the invention.

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Synthesis and biological screening of some novel 6-substituted 2-alkylpyridazin-3(2H)-ones as anti-inflammatory and analgesic agents

Some novel derivatives of 2-alkyl 6-substituted pyridazin-3(2H)-ones were synthesized by condensation of 3,6-dichloropyridazine with the sodium salt of benzyl cyanide, followed by hydrolysis and coupling with alkyl halides. The synthesized compounds were screened as cyclooxygenase (COX)-1/COX-2 inhibitors and as analgesic and anti-inflammatory agents. Among the synthesized compounds, 6-benzyl-2-methylpyridazin-3(2H)-one (4a), 6-benzoyl-2-propylpyridazin-3(2H)-one (8b), and 6-(hydroxy(phenyl)methyl)-2-methylpyridazin-3(2H)-one (9a) displayed the highest COX-2 selectivity indices of 96, 99, and 98, respectively, and analgesic efficacies of 47%, 46%, and 45% protection, respectively. Also, compounds 4a, 8b, and 9a showed anti-inflammatory activities of 65%, 60%, and 62% inhibition of edema, respectively, at a dose of 10 mg/kg, which is higher than that of diclofenac (58% inhibition of edema).

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Synthesis, crystal structures and properties of two copper (II) complexes with pyridazine derivative ligand

Two new complexes, [Cu(L)2(CH3OH)]¡¤(ClO 4)2 (1) and [Cu(L)2(H2O)] ¡¤(NO3)2 (2), have been synthesized and their crystal structures have been determined by X-ray analysis, where L = 3-(3,5-bimethylpyrazole-yl)-6-chloro-pyridazine]. The complex 1 crystallizes in the monoclinic, space group C2/c, and the coordination configuration of copper (II) is better described as trigonal pyramidal geometry with four N atoms from L and one O methanol . The coordination configuration of 2 is quite similar to that of 1 except Owater instead of O methanol . The intermolecular hydrogen bonds link the repeat units and extend the molecules to multinuclear structures in both compounds. The spectral properties of the title compounds have been studied and discussed. Furthermore, the antibacterial activities of the title compounds have been detected, the results indicate that the ligands and two copper(II) complexes exhibit certain fungicidal activities again several bacteria.

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3(2H)-pyridazinone derivatives, a process and intermediates for preparing them and medicaments containing them and/or other 3(2H)-pyridazinone derivatives

The subject-matter of the invention are 3(2H)-Pyridazinone derivatives of the general formula wherein R stands for an ethyl or propyl group substituted by a terminal halogen atom or hydroxyl group or a terminal group of the formula in which latter R? represents a hydrogen atom or an optionally substituted benzyl group and R? represents a hydrogen atom or an optionally substituted benzo[1,4]dioxan-2-yl-methyl or benzo[1,4]dioxan-2-yl-ethyl group or a group of the formula in which latter n is 2 or 3 and R? stands for an optionally substituted phenoxy or phenylthio group and X stands for a hydrogen or halogen atom or an optionally substituted saturated or unsaturated 5-or 6-membered heterocyclic group.Furthermore the subject-matter of the invention are a process and intermediates for preparing these compounds and medicaments containing them and/or other 3(2H)-pyridazinone derivatives.The compounds according to the invention inhibit the adrenergic alpha? receptors, have a calcium–antagonistic effect and exert blood pressure lowering action.

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