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Piperadinyl-substituted pyridylalkane, alkene and alkine carboxamides

The invention relates to new piperidinyl-substituted pyridyl carboxamides of the general formula (I), wherein the structure element E has meanings (E1) or (E2) and whereby the heterocyclic ring can optionally have a double bond. These substances have especially high cytostatic activities and pronounced immunosuppressive properties which make them suitable for therapeutic treatment in broad tumor spectrum.

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Pyridazine -3- formamide compound, preparation method and application thereof in medicine and pharmacy (by machine translation)

The invention relates to a method for the treatment and Janus or prevention of (JAK), kinase 2(TYK2), in particular tyrosine kinase, of a compound or a pharmaceutically acceptable salt. thereof, in particular, or a pharmaceutically acceptable salt thereof, to a pharmaceutical composition (I) containing said compound or a pharmaceutically acceptable salt thereof, and a process for the preparation of said compound or a pharmaceutically acceptable salt of said compound or a pharmaceutically acceptable salt of said compound or a pharmaceutically acceptable salt of, said compound or a pharmaceutically acceptable salt of said compound or a solvate thereof, and a. pharmaceutically acceptable salt of said compound, The. compound of formula Janus or a pharmaceutically acceptable salt thereof, according (I) to claim. (by machine translation)

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Heterocyclic Compounds and Methods of Use

This disclosure provides compounds and methods of using those compounds to treat metabolic disorders and hyperproliferative disorders, including administration of the compounds in conjunction with hormone receptor antagonists.

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AZABENZIMIDAZOLE DERIVATIVES AS PI3K BETA INHIBITORS

The present invention relates to azabenzimidazole derivatives of Formula (I) (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as pI3Kbeta inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active 10 ingredient as well as the use of said compounds as a medicament.

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SUBSTITUTED TRIAZOLOPYRIDINES

The present invention relates to substituted triazolopyridine compounds of general formula (I) : in which R1, R2, R3, R4, and R5 are as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease of uncontrolled cell growth, proliferation and/or survival as well as to the use of intermediate compounds for the preparation of said compounds.

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SOLUBILIZED THIAZOLOPYRIDINES

Provided herein are novel sirtuin-modulating compounds Structural Formula (I): and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benfit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent

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Special ergolines efficiently inhibit the chemokine receptor CXCR3 in blood

The structure-activity relationship of highly potent special ergolines which selectively block the chemokine receptor CXCR3 is reported. The most potent compounds showed IC50 values below 10 nM in both ligand binding and Ca2+-mobilization assays. However, these compounds were poorly active in an assay that measures receptor occupancy in blood. Introduction of polar substituents led to derivatives with IC50 values below 10 nM in this assay. Among them was compound 11a which showed both a favorable PK profile and cross reactivity with rodent CXCR3 making it a promising tool compound to further explore the role of CXCR3 in animal models.

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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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