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Several strategies have been employed to reduce the long in vivo half-life of our lead CB1 antagonist, triazolopyridazinone 3, to differentiate the pharmacokinetic profile versus the lead clinical compounds. An in vitro and in vivo clearance data set revealed a lack of correlation; however, when compounds with <5% free fraction were excluded, a more predictable correlation was observed. Compounds with log P between 3 and 4 were likely to have significant free fraction, so we designed compounds in this range to give more predictable clearance values. This strategy produced compounds with desirable in vivo half-lives, ultimately leading to the discovery of compound 46. The progression of compound 46 was halted due to the contemporaneous marketing and clinical withdrawal of other centrally acting CB1 antagonists; however, the design strategy successfully delivered a potent CB1 antagonist with the desired pharmacokinetic properties and a clean off-target profile. If you are interested in 932-22-9, you can contact me at any time and look forward to more communication. Safety of 4,5-Dichloro-3(2H)-pyridazinone

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A novel series of 4-pyridazin-3-one and 5-pyridazin-3-one analogues were designed and synthesized as H3R antagonists. Structure-activity relationship revealed the 5-pyridazin-3-ones 8a and S-methyl 8b had excellent human and rat H3R affinities, and acceptable pharmacokinetic properties. In vivo evaluation of 8a showed potent activity in the rat dipsogenia model and robust wake-promoting activity in the rat EEG/EMG model.

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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 932-22-9, name is 4,5-Dichloro-3(2H)-pyridazinone, introducing its new discovery. category: pyridazine

The present invention relates to imidazopyridazine derivatives. More particularly, it relates to 4-(biphenyl-3-yl)-7H-imidazo[4,5-c]pyridazine derivatives of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 and R5 are as defined in the description. The imidazopyridazine derivatives of the present invention modulate the activity of the GABAA receptor. They are useful in the treatment of a number of conditions, including pain.

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A new method for the traceless solid phase synthesis of 3(2H)-pyridazinones has been developed employing dihydropyran-functionalized resin. The procedure has permitted the preparation of several diarylpyridazinones through a Suzuki cross-coupling reaction and cleavage conditions that promoted a retro-ene fragmentation.

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The present invention relates to a pyridazinone derivative which can be used as a caspase inhibitor, process for the preparation thereof, and pharmaceutical composition for inhibiting caspase comprising the same.

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The present invention relates to pyridazinones and related compounds which are inhibitors of PARP7 and are useful in the treatment of cancer.

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Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, R1, R2, R3, R4, R5, Ra and Rb are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with the P2X7 purinergic receptor.

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Theophylline derivatives with several groups linked at the 7-position were synthesized and their pharmacological activities were studied on guinea pig. Relaxant action in the tracheal muscle was increased in comparison with that of theophylline when the 3(2H)-pyridazinone system was linked to 7-(2-ethyl)-theophylline through the piperazine ring, but decreased when the 7-(2-ethyl)-theophylline was linked to 3(2H)-pyridazinone ring through an amino group.

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Amyloid plaques, which are primarily composed of aggregated amyloid-beta (Abeta) peptide, are the neuropathological hallmarks of Alzheimer’s disease (AD). Fluorescent markers containing 2-styrylpyridazin-3(2H)-ones were developed to detect intracellular aggregated Abeta peptides. Nine compounds exhibited a greater than 10-fold increase of in emission spectra before and after mixing with Abeta aggregates compared with before mixing. Among these compounds, compound 9n exhibited the highest affinity for Abeta aggregates (Kd = 1.84 muM) and selectively stained both aggregated intracellular Abeta and Abeta plaques in the transgenic AD model mice (APP/PS1). These preliminary results indicate that 2-styrylpyridazin-3(2H)-one derivatives are promising alternative fluorescence imaging agent for the study of AD.

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Easily accessible 2-substituted 4-aryl-5-methoxy- and 2-substituted 5-aryl-4-methoxypyridazin-3(2H)-ones were transformed into the corresponding aryl-hydroxypyridazin-3(2H)-ones by alkaline hydrolysis. The use of these compounds in the synthesis of 2-substituted 4,5-diarylpyridazin-3(2H)-ones with two differently substituted aryl groups was investigated. Two aryl-hydroxypyridazin-3(2H)-ones, 2-(2-benzyl-5-hydroxy-3-oxo-2,3-dihydropyridazin-4-yl)benzaldehyde and 2-(1-benzyl-5-hydroxy-6-oxo-1,6-dihydropyridazin-4-yl)benzaldehyde, were transformed into 2-benzyl-1H-isochromeno[3,4-d]pyridazine-1,6(2H)-dione and 3-benzyl-3H-isochromeno[3,4-d]pyridazine-4,6-dione, respectively, via oxidation of the formyl group with KMnO4 followed by lactonization.

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