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Compound M & B 39890A [N-(3-imidazol-1-ylpropyl)-2- (3-trifluoromethylbenzenesulphonamido)benzamide hydrochloride] had no effect on cellular cAMP and cGMP levels but significantly inhibited insulin and glucagon secretion from freshly isolated normal rat islets stimulated with 10 mM glucose and 20 mM
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The identification of a novel series of benzamide-containing MCHr1 antagonists is described. Compound 22 displayed moderate efficacy in a diet induced obesity mice model.
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Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of insulin signaling, is considered as a promising and validated therapeutic target for type 2 diabetes mellitus (T2DM) and obesity. Upon careful study, a series of 2-ethoxy-4-(methoxymethyl)benzamide and
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In this study, the adipogenesis-suppressing effect of 3,5-dimethoxy(4-methoxyphenyl)benzamide (DMPB), a derivative of the anti-obesity substance resveratrol, was measured in 3T3-L1 cells. The results show that DMPB effectively suppressed the hormone-induced differentiation of 3T3-L1 cells, compared
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Leptin, the product of the obese gene, is an adipocyte-secreted protein hormone playing a key role in the progression of obesity and hepatic steatosis. In this study, 28 novel (thio)urea and guanidine-based analogues have been synthesized and
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A substituted 4-aminopiperidine was identified as showing activity in an MCH assay from an HTS effort. Subsequent structural modification of the scaffold led to the identification of a number of active MCH antagonists. 3,5-Dimethoxy-N-(1-(naphthalen-2-ylmethyl)piperidin-4-yl)benzamide (5c) was among
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p-[(R)-3-[bis-[(R)-beta-hydroxyphenethyl]amino]butyl]benzamide (Ro 16-8714/000) is one of the most effective compounds, of a new series of calorigenic bis-phenethanolamine derivatives, which combine anti-obesity and antidiabetic qualities. Ro 16-8714 exhibited potent stimulation of oxygen
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Compound LY104119, [R-(R*,S*)]-4-[3-[(2-hydroxy-2-phenylethyl)amino]butyl]benzamide monohydrochloride, was found to be a potent beta-agonist in the mouse. Its Ki for displacing the binding of (-)-3H-dihydroalprenolol to beta-receptors on the lung membranes from either viable yellow obese mice
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GPR139 is an orphan class A G protein-coupled receptor found mainly in the central nervous system. It has its highest expression levels in the hypothalamus and striatum, regions regulating metabolism and locomotion, respectively, and has therefore been suggested as a potential target for obesity and
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Recently, we discovered 3-aminomethylquinoline derivative 1, a selective, highly potent, centrally acting, and orally bioavailable human MCH receptor 1 (hMCHR1) antagonist, that inhibited food intake in F344 rats with diet-induced obesity (DIO). Subsequent investigation of 1 was discontinued because
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