thiophene/затлъстяване

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Discovery of 1-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-4-((pyrrolidine-1-sulfonamido)methyl)-5-(5-((4-(trifluoromethyl)phenyl)ethynyl)thiophene-2-yl)-1H-pyrazole-3-carboxamide as a novel peripherally restricted cannabinoid-1 receptor antagonist with significant weight-loss efficacy in diet-induced obese mice.

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After extensive synthetic efforts, we found that many structurally diverse bioisosteres could be generated via derivatizing the C-4 alkyl chain on the pyrazole ring of compound 3 (B/P = 1/33) with different electronegative groups. Especially when a sulfonamide or sulfamide moiety was added,

Potent and selective thiophene urea-templated inhibitors of S6K.

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S6K1 (p70 S6 kinase-1) is thought to play a critical role in the development of obesity and insulin resistance, thus making it an attractive target in developing medicines for the treatment of these disorders. We describe a novel thiophene urea class of S6K inhibitors. The lead matter for the

Design, synthesis and in vitro evaluation of novel benzo[b]thiophene derivatives as serotonin N-acetyltransferase (AANAT) inhibitors.

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Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) is the penultimate enzyme in melatonin (5-methoxy-N-acetyltryptamine) biosynthesis. It is the key-enzyme responsible of the nocturnal rhythm of melatonin production in the pineal gland. Specific AANAT inhibitors could be

2-(3-Benzoylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ameliorates metabolic disorders in high-fat diet-fed mice.

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OBJECTIVE Sterol-regulatory element binding proteins (SREBPs) are major transcription factors that regulate liver lipid biosynthesis. In this article we reported a novel synthetic compound 2-(3-benzoylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (ZJ001) that inhibited the

A thienopyridazinone-based melanin-concentrating hormone receptor 1 antagonist with potent in vivo anorectic properties.

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Melanin-concentrating hormone receptor antagonists containing thieno- and a benzopyridazinone cores were designed and tested as potential anorectic agents. These ligands showed high affinity for the receptor, potent functional activity in vitro, and good oral bioavailabilty in rats. The thiophene

Slowed gastric emptying and improved oral glucose tolerance produced by a nanomolar-potency inhibitor of calcium-activated chloride channel TMEM16A.

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Interstitial cells of Cajal, which express the calcium-activated chloride channel transmembrane member 16A (TMEM16A), are an important determinant of gastrointestinal (GI) motility. We previously identified the acylaminocycloalkylthiophene class of TMEM16A inhibitors, which, following medicinal

Antiobesity effects of a novel lipid synthesis inhibitor (Ro 22-0654).

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The present studies were conducted to determine the antiobesity effects of a novel inhibitor of hepatic fatty acid synthesis, 4-amino-5-ethyl-3-thiophene-carboxylic acid methyl ester hydrochloride (Ro 22-0654/001). Weight gain was decreased by treatment with Ro 22-0654 in Sprague Dawley and in lean

Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel 1-(1H-benzimidazol-6-yl)pyridin-2(1H)-one derivatives and design to avoid CYP3A4 time-dependent inhibition.

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Melanin-concentrating hormone (MCH) is an attractive target for antiobesity agents, and numerous drug discovery programs are dedicated to finding small-molecule MCH receptor 1 (MCHR1) antagonists. We recently reported novel pyridine-2(1H)-ones as aliphatic amine-free MCHR1 antagonists that

An alpha7 nicotinic acetylcholine receptor-selective agonist reduces weight gain and metabolic changes in a mouse model of diabetes.

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Type 2 diabetes has become a pervasive public health problem. The etiology of the disease has not been fully defined but appears to involve abnormalities in peripheral and central nervous system pathways, as well as prominent inflammatory components. Because nicotinic acetylcholine receptors

A family of push-pull bio-probes for tracking lipid droplets in living cells with the detection of heterogeneity and polarity.

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Lipid droplets (LDs) are multi-functional organelles with the storage of lipid and participating in a variety of physiological processes, including membrane transport and signal transduction. The dysfunction of LDs has been reported to be associated with multiple diseases such as obesity, diabetes,

7-Chloroarctinone-b as a new selective PPARgamma antagonist potently blocks adipocyte differentiation.

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OBJECTIVE Peroxisome proliferator-activated receptor gamma (PPARgamma) is a therapeutic target for obesity, cancer and diabetes mellitus. In order to develop potent lead compounds for obesity treatment, we screened a natural product library for novel PPARgamma antagonists with inhibitory effects on

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