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Discovery and optimization of 1-(4-(Pyridin-2-yl)benzyl)imidazolidine-2,4- dione derivatives as a novel class of selective cannabinoid CB2 receptor agonists

Here, we report the identification and optimization of 1-(4-(pyridin-2-yl) benzyl)imidazolidine-2,4-dione derivatives as a novel chemotype with selective cannabinoid CB2 receptor agonist activity. 1 is a potent and selective cannabinoid CB2 receptor agonist (hCB2 pEC50 = 8.6). The compound was found to be metabolically unstable, which resulted in low oral bioavailability in rat (Fpo = 4%) and possessed off-target activity at the hERG ion channel (pKi = 5.5). Systematic modification of physicochemical properties, such as lipophilicity and basicity, was used to optimize the pharmacokinetic profile and hERG affinity of this novel class of cannabinoid CB2 receptor agonists. This led to the identification of 44 as a potent, selective, and orally bioavailable cannabinoid CB2 receptor agonist (hCB2 pEC50 = 8.0; hERG pKi < 4; Fpo = 100%), which was active in a rat spinal nerve ligation model of neuropathic pain. Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.Reference of 39093-93-1. In my other articles, you can also check out more blogs about 39093-93-1

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ISOXAZOLO-PYRIDAZINE DERIVATIVES

The invention relates to isoxazolo-pyridazine compounds, in particular those of formula I as described above and to a pharmaceutically acceptable salts thereof, having affinity and selectivity for the GABA A alpha5 receptor binding site, their manufacture, pharmaceutical compositions containing them and their use as cognitive enhancers or for the treatment of cognitive disorders like Alzheimer”s disease.

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OXADIAZOLE DERIVATIVES WITH CRTH2 RECEPTOR ACTIVITY

Compounds of formula (I) are CRTH2 ligands, useful for treatment of inflammatory, autoimmune, respiratory or allergy disease: wherein R1 is hydrogen or methyl and R2 is optionally substituted cycloalkyl, or optionally substituted non-aromatic heterocyclyl having 4 to 6 ring atoms; or R1 and R2, taken together with the carbon atom to which they are attached form an optionally substituted cycloalkyl, or optionally substituted non-aromatic heterocyclyl ring having 4 to 6 ring atoms; R is hydrogen or an optional substituent; the phenyl ring containing the substituent R is optionally substituted by 1 , 2 or 3 optional substituents; A is hydrogen or C1-C3 alkyl; and ring Ar is an optionally substituted phenyl or 5- or 6- membered monocyclic heteroaryl ring.

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PYRIMIDINE TauBetaKappa/IotaKappaKappaepsilon INHIBITOR COMPOUNDS AND USES THEREOF

The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TauBetaKappa/IotaKappaKappaepsilon inhibitors.

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GLYCINE COMPOUND

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that a compound of the present invention or a salt thereof exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. The present invention further relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound of the present invention or a salt thereof, and an excipient.

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Substituted Adipan acid derivatives (II) (by machine translation)

The invention relates to substituted phenylalanine derivatives and to processes for preparation thereof, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of cardiovascular disorders and/or severe perioperative blood loss.

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DIAZEPANE COMPOUNDS WHICH MODULATE THE CB2 RECEPTOR

Compounds of formula (I) are disclosed. Compounds according to the invention bind to and are agonists, antagonists or inverse agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.

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SULFUR-CONTAINING BICYCLIC COMPOUND

A sulfur-containing bicyclic compound having a PAM action of GABAB, and it use for preventing and/or treating schizophrenia, CIAS, cognitive impairment, fragile X syndrome, autism spectrum disorder, spasticity, anxiety disorder, substance addiction, pain, fibromyalgia, or Charcot-Marie-Tooth disease. A pharmaceutical composition for preventing and/or treating schizophrenia, cognitive impairment associated with schizophrenia (CIAS), cognitive impairment, fragile X syndrome, autism spectrum disorder, spasticity, anxiety disorder, substance addiction, pain, fibromyalgia, Charcot-Marie-Tooth disease, or the like, which has a positive allosteric modulator (PAM action) of GABAB.

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NEW TETRACYCLIC COMPOUNDS

This disclosure relates to new tetracyclic compounds that may be used to modulate a histamine receptor in an individual. The compounds in one embodiment are tetracyclic [4,3- b]indoles. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

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PYRAZOLE COMPOUNDS

Compounds of formula (I): wherein R1, R2, R3, R4, R5, and X are defined herein. Also disclosed are pharmaceutical compositions and methods related to use of these compounds.

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