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C Crone J Frokjaer-Jensen JJ Friedman O Christensen 《The Journal of general physiology》1978,71(2):195-220
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Guohua Zhao Chet Kwon Sharon N. Bisaha Philip D. Stein Karen A. Rossi Xueying Cao Thao Ung Ginger Wu Chen-Pin Hung Sarah E. Malmstrom Ge Zhang Qinling Qu Jinping Gan William J. Keim Mary Jane Cullen Kenneth W. Rohrbach James Devenny Mary Ann Pelleymounter Jeffrey A. Robl 《Bioorganic & medicinal chemistry letters》2013,23(13):3914-3919
The 5-HT2C receptor has been implicated as a critical regulator of appetite. Small molecule activation of the 5-HT2C receptor has been shown to affect food intake and regulate body weight gain in rodent models and more recently in human clinical trials. Therefore, 5-HT2C is a well validated target for anti-obesity therapy. The synthesis and structure–activity relationships of a series of novel tetrahydropyrazinoisoquinolinone 5-HT2C receptor agonists are presented. Several members of this series were identified as potent 5-HT2C receptor agonists with high functional selectivity against the 5-HT2A and 5-HT2B receptors and reduced food intake in an acute rat feeding model upon oral dosing. 相似文献
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Atwal KS Ahmad S Ding CZ Stein PD Lloyd J Hamann LG Green DW Ferrara FN Wang P Rogers WL Doweyko LM Miller AV Bisaha SN Schmidt JB Li L Yost KJ Lan HJ Madsen CS 《Bioorganic & medicinal chemistry letters》2004,14(4):1027-1030
A series of substituted guanidine derivatives were prepared and evaluated as potent and selective inhibitors of mitochondrial F(1)F(0) ATP hydrolase. The initial thiourethane derived lead molecules possessed intriguing in vitro pharmacological profiles, though contained moieties considered non-drug-like. Analogue synthesis efforts led to compounds with maintained potency and superior physical properties. Small molecules in this series which potently and selectivity inhibit ATP hydrolase and not ATP synthase may have utility as cardioprotective agents. 相似文献
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Shi Y O'Connor SP Sitkoff D Zhang J Shi M Bisaha SN Wang Y Li C Ruan Z Lawrence RM Klei HE Kish K Liu EC Seiler SM Schweizer L Steinbacher TE Schumacher WA Robl JA Macor JE Atwal KS Stein PD 《Bioorganic & medicinal chemistry letters》2011,21(24):7516-7521
The design, synthesis and SAR of a novel class of valerolactam-based arylsulfonamides as potent and selective FXa inhibitors is reported. The arylsulfonamide–valerolactam scaffold was derived based on the proposed bioisosterism to the arylcyanoguanidine-caprolactam core in known FXa inhibitors. The SAR study led to compound 46 as the most potent FXa inhibitor in this series, with an IC50 of 7 nM and EC2×PT of 1.7 μM. The X-ray structure of compound 40 bound to FXa shows that the sulfonamide–valerolactam scaffold anchors the aryl group in the S1 and the novel acylcytisine pharmacophore in the S4 pockets. 相似文献
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