Category: 360575-29-7

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Structure-activity relationship study of novel NR2B-selective antagonists with arylamides to avoid reactive metabolites formation

A novel potent NMDA-NR2B selective antagonist (5b) without the reactive metabolites formation issue was identified. Through this study, a close correlation between reactive metabolites formation and calculated HOMO energies of parent compounds was found.

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SPIROINDOLINONES AS DDR1 INHIBITORS

The present invention relates to compounds of formula (I): or pharmaceutically acceptable salts thereof, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments.

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Benzothiophene – Wikipedia,
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Synthetic Route of 360575-29-7, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 360575-29-7, molcular formula is C10H7BrO2S, introducing its new discovery.

Indazole-and indole-5-carboxamides: Selective and reversible monoamine oxidase B inhibitors with subnanomolar potency

Indazole-and indole-carboxamides were discovered as highly potent, selective, competitive, and reversible inhibitors of monoamine oxidase B (MAO-B). The compounds are easily accessible by standard synthetic procedures with high overall yields. The most potent derivatives were N-(3,4- dichlorophenyl)-1-methyl-1H-indazole-5-carboxamide (38a, PSB-1491, IC 50 human MAO-B 0.386 nM, >25000-fold selective versus MAO-A) and N-(3,4-dichlorophenyl)-1H-indole-5-carboxamide (53, PSB-1410, IC50 human MAO-B 0.227 nM, >5700-fold selective versus MAO-A). Replacement of the carboxamide linker with a methanimine spacer leading to (E)-N-(3,4- dichlorophenyl)-1-(1H-indazol-5-yl)methanimine (58) represents a further novel class of highly potent and selective MAO-B inhibitors (IC50 human MAO-B 0.612 nM, >16000-fold selective versus MAO-A). In N-(3,4- difluorophenyl-1H-indazole-5-carboxamide (30, PSB-1434, IC50 human MAO-B 1.59 nM, selectivity versus MAO-A >6000-fold), high potency and selectivity are optimally combined with superior physicochemical properties. Computational docking studies provided insights into the inhibitors’ interaction with the enzyme binding site and a rationale for their high potency despite their small molecular size.

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Because a catalyst decreases the height of the energy barrier, 360575-29-7, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.360575-29-7, Name is Methyl 4-bromobenzo[b]thiophene-2-carboxylate, molecular formula is C10H7BrO2S. In a article£¬once mentioned of 360575-29-7

Synthesis of unprotected carboxy indazoles via Pd-catalyzed carbonylation

The first published synthesis of unprotected carboxy indazoles from the corresponding bromoindazoles is described. This is achieved via Pd(II)-catalyzed carbonylation and is demonstrated to work on a variety of indazoles.

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Chemistry, like all the natural sciences, begins with the direct observation of nature¡ª in this case, of matter. Recommanded Product: Methyl 4-bromobenzo[b]thiophene-2-carboxylate, C10H7BrO2S. A document type is Article, introducing its new discovery., Recommanded Product: Methyl 4-bromobenzo[b]thiophene-2-carboxylate

Synthesis of spiropiperidine lactam acetyl-CoA carboxylase inhibitors

The synthesis of 4?,6?-dihydrospiro[piperidine-4,5?- pyrazolo[3,4-c]pyridin]-7?(2?H)-one-based acetyl-CoA carboxylase inhibitors is reported. The hitherto unknown N-2 tert-butyl pyrazolospirolactam core was synthesized from ethyl 3-amino-1H-pyrazole-4-carboxylate in a streamlined 10-step synthesis requiring only one chromatography procedure. The described synthetic strategy provides pyrazolo-fused spirolactams from halogenated benzylic arenes and cyclic carboxylates. Key steps include a regioselective pyrazole alkylation providing the N-2 tert-butyl pyrazole and a Curtius rearrangement under both conventional and flow conditions to install the hindered amine via a stable and isolable isocyanate. Finally, a Parham-type cyclization was used to furnish the desired spirolactam. An analogous route provided efficient access to the related N-1 isopropyl lactam series. Elaboration of the lactam cores via amidation enabled synthesis of novel ACC inhibitors and the identification of potent analogues.

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Benzothiophene – Wikipedia,
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Reference of 360575-29-7, Chemistry is the experimental science by definition. We want to make observations to prove hypothesis. For this purpose, we perform experiments in the lab. 360575-29-7, Name is Methyl 4-bromobenzo[b]thiophene-2-carboxylate,introducing its new discovery.

INHIBITORS OF DIHYDROCERAMIDE DESATURASE FOR TREATING DISEASE

Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic, cardiovascular, fibrotic, autoimmune/chronic inflammatory diseases, cystic fibrosis, various cancers, neurodegenerative diseases, lipid storage disorders, and ischemia/reperfusion injury, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.

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INDAZOLES

The invention provides novel substituted indazole compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases such as cancer, inflammatory or degenerative diseases.

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Chemistry is traditionally divided into organic and inorganic chemistry. SDS of cas: 360575-29-7, The former is the study of compounds containing at least one carbon-hydrogen bonds.In a patent£¬Which mentioned a new discovery about 360575-29-7

Novel Human Aminopeptidase N Inhibitors: Discovery and Optimization of Subsite Binding Interactions

Aminopeptidase N (APN/CD13) is a zinc-dependent M1 aminopeptidase that contributes to cancer progression by promoting angiogenesis, metastasis, and tumor invasion. We have previously identified hydroxamic acid-containing analogues that are potent inhibitors of the APN homologue from the malarial parasite Plasmodium falciparum M1 aminopeptidase (PfA-M1). Herein, we describe the rationale that underpins the repurposing of PfA-M1 inhibitors as novel APN inhibitors. A series of novel hydroxamic acid analogues were developed using a structure-based design approach and evaluated their inhibition activities against APN. N-(2-(Hydroxyamino)-2-oxo-1-(3?,4?,5?-trifluoro-[1,1?-biphenyl]-4-yl)ethyl)-4-(methylsulfonamido)benzamide (6ad) proved to be an extremely potent inhibitor of APN activity in vitro, selective against other zinc-dependent enzymes such as matrix metalloproteases, and possessed limited cytotoxicity against Ad293 cells and favorable physicochemical and metabolic stability properties. The combined results indicate that compound 6ad may be a useful lead for the development of anticancer agents.

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Benzothiophene – Wikipedia,
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Catalysts allow a reaction to proceed via a pathway that has a lower activation energy than the uncatalyzed reaction. In heterogeneous catalysis, catalysts provide a surface to which reactants bind in a process of adsorption. 360575-29-7, name is Methyl 4-bromobenzo[b]thiophene-2-carboxylate. In an article£¬Which mentioned a new discovery about 360575-29-7, name: Methyl 4-bromobenzo[b]thiophene-2-carboxylate.

LINEAR GLYCOSIDASE INHIBITORS

Compounds of formula (I) wherein A, R, W, Q, L, n and m have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer’s disease.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

Reference of 360575-29-7, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.360575-29-7, Name is Methyl 4-bromobenzo[b]thiophene-2-carboxylate, molecular formula is C10H7BrO2S. In a article£¬once mentioned of 360575-29-7

Decreasing the rate of metabolic ketone reduction in the discovery of a clinical acetyl-CoA carboxylase inhibitor for the treatment of diabetes

Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. An advanced series of spirocyclic ketone-containing ACC inhibitors recently reported by Pfizer were metabolized in vivo by ketone reduction, which complicated human pharmacology projections. We disclose that this metabolic reduction can be greatly attenuated through introduction of steric hindrance adjacent to the ketone carbonyl. Incorporation of weakly basic functionality improved solubility and led to the identification of 9 as a clinical candidate for the treatment of T2DM. Phase I clinical studies demonstrated dose-proportional increases in exposure, single-dose inhibition of de novo lipogenesis (DNL), and changes in indirect calorimetry consistent with increased whole-body fatty acid oxidation. This demonstration of target engagement validates the use of compound 9 to evaluate the role of DNL in human disease.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem