Discovery of 2H-Pyran-3,5(4H,6H)-dione

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Palladium-catalyzed N-monoarylation of amidines and a one-pot synthesis of quinazoline derivatives

A method for the Pd-catalyzed N-arylation of both aryl and alkyl amidines with a wide range of aryl bromides, chlorides, and triflates is described. The reactions proceed in short reaction times and with excellent selectivity for monoarylation. A one-pot synthesis of quinazoline derivatives, via addition of an aldehyde to the crude reaction mixture following Pd-catalyzed N-arylation, is also demonstrated.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

New explortion of Ethyl 2-((tetrahydro-2H-pyran-2-yl)oxy)acetate

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First Total Synthesis of (+/-)-Oxerine

Total synthesis of (+/)-oxerine (1), a monoterpene alkaloid, starting from 3-bromopyridine (7) is described.The key reaction in this sequence is the samarium iodide (SmI2)-mediated intramolecular cyclization of gamma-ethynyl bromide (4).

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The important role of 19752-84-2

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Discovery of Selective Small Molecule Inhibitors of Monoacylglycerol Acyltransferase 3

Inhibition of triacylglycerol (TAG) biosynthetic enzymes has been suggested as a promising strategy to treat insulin resistance, diabetes, dyslipidemia, and hepatic steatosis. Monoacylglycerol acyltransferase 3 (MGAT3) is an integral membrane enzyme that catalyzes the acylation of both monoacylglycerol (MAG) and diacylglycerol (DAG) to generate DAG and TAG, respectively. Herein, we report the discovery and characterization of the first selective small molecule inhibitors of MGAT3. Isoindoline-5-sulfonamide (6f, PF-06471553) selectively inhibits MGAT3 with high in vitro potency and cell efficacy. Because the gene encoding MGAT3 (MOGAT3) is found only in higher mammals and humans, but not in rodents, a transgenic mouse model expressing the complete human MOGAT3 was used to characterize the effects of 6f in vivo. In the presence of a combination of diacylglycerol acyltransferases 1 and 2 (DGAT1 and DGAT2) inhibitors, an oral administration of 6f exhibited inhibition of the incorporation of deuterium-labeled glycerol into TAG in this mouse model. The availability of a potent and selective chemical tool and a humanized mouse model described in this report should facilitate further dissection of the physiological function of MGAT3 and its role in lipid homeostasis.

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Final Thoughts on Chemistry for Tetrahydro-2H-pyran-4-ol

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Synthesis and anti-cancer activity of ND-646 and its derivatives as acetyl-CoA carboxylase 1 inhibitors

Acetyl-coA carboxylase 1 (ACC1) is the first and rate-limiting enzyme in the de novo fatty acid synthesis (FASyn) pathway. In this study, through public database analysis and clinic sample test, we for the first time verified that ACC1 mRNA is overexpressed in non-small-cell lung cancer (NSCLC), which is accompanied by reduced DNA methylation at CpG island S shore of ACC1. Our study further demonstrated that higher ACC1 levels are associated with poor prognosis in NSCLC patients. Besides, we developed a novel synthetic route for preparation of a known ACC inhibitor ND-646, synthesized a series of its derivatives and evaluated their activity against the enzyme ACC1 and the A549 cell. As results, most of the tested compounds showed potent ACC1 inhibitory activity with IC50 values 3?10 nM. Among them, compounds A2, A7 and A9 displayed strong cancer inhibitory activity with IC50 values 9?17 nM by impairing cell growth and inducing cell death. Preliminary SAR analysis clearly suggested that (R)-configuration and amide group were vital to ACC1 and A549 inhibition, since compound (S)-A1 (the enantiomer of ND-646) had poor activity of ACC1 inhibition and the carboxylic acid ND-630 almost lost anticancer effect on A549 cells. Collectively, these findings indicate that ACC1 is a potential biomarker and target for non-small-cell lung cancer, and ND-646 and its derivatives as ACC1 inhibitors deserve further study for treatment of NSCLC.

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More research is needed about 50675-18-8

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IMIDAZOPIPERAZINE INHIBITORS OF TRANSCRIPTION ACTIVATING PROTEINS

The present disclosure relates to heterocyclic compounds and methods which may be useful as inhibitors of transcription activating proteins such as CBP and P300 for the treatment or prevention of diseases such as proliferative diseases, inflammatory disorders, autoimmune diseases, and fibrotic diseases.

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Tetrahydropyran – Wikipedia,
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Top Picks: new discover of Tetrahydro-2H-pyran-4-ol

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Highly selective c-Jun N-terminal kinase (JNK) 2 and 3 inhibitors with in vitro CNS-like pharmacokinetic properties prevent neurodegeneration

In this Letter, we describe the discovery of selective JNK2 and JNK3 inhibitors, such as 10, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs, p38alpha and ERK2. Substitution of the naphthalene ring affords an isoform selective JNK3 inhibitor, 30, with approximately 10-fold selectivity over both JNK1 and JNK2. A naphthalene ring penetrates deep into the selectivity pocket accounting for the differentiation amongst the kinases. Interestingly, the gatekeeper Met146 sulfide interacts with the naphthalene ring in a sulfur-pi stacking interaction. Compound 38 ameliorates neurotoxicity induced by amyloid-beta in human cortical neurons. Lastly, we demonstrate how to install propitious in vitro CNS-like properties into these selective inhibitors.

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Awesome and Easy Science Experiments about 2081-44-9

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Synthesis of n-alkyl terminal halohydrin esters from acid halides and cyclic ethers or thioethers under solvent- and catalyst-free conditions

An efficient and eco-friendly protocol has been developed for the preparation of n-alkyl terminal halohydrin esters under solvent- and catalyst-free conditions. Ring opening of cyclic ethers by organic acid halides affords the 1,4- and 1,5-halohydrins, OH-protected by different acyl groups. The green reaction conditions, simple work-up procedures, high yields and broad substrate scope of the reaction highlight the positive features of this method. This journal is

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Simple exploration of Tetrahydro-2H-pyran-4-amine hydrochloride

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AMIDES AS PIM INHIBITORS

The invention relates to amide-containing compounds of formula (1), and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer

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Geminal carboxylic acids and esters thereof, pharmaceutical formulations containing them useful in the treatment of bone dysmetabolism

Compounds of formula I: wherein Ra, Rb, Phi, B and R are as defined in the disclosure, have antagonistic activity on osteoclast hyper-reactivity.

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New phenylbenzamide imidazolecarboxylic compd. (by machine translation)

PROBLEM TO BE SOLVED: neurodegeneratively dermatopathy medicinal therapeutic agent such as practicable chromogen storage stability and safety and a compound having a pharmaceutical composition containing the compound. SOLUTION: eq. (1) ( In the formula, R is C 1-6 represents an alkyl group, X is, O or S ;, the Y, fumaric acid, citric acid, malic acid, succinic acid; and organic acid selected from, n the 0-5 (however, not n is 0). ) And a compound represented by the pharmaceutical composition comprising a compound. Selected drawing: no (by machine translation)

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics