58586-55-3Relevant articles and documents
Preparation and application of triazole compound
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Paragraph 0073; 0074; 0075, (2017/07/22)
The invention provides preparation and application of a triazole compound. A preparation method comprises the following steps: enabling a first compound, namely 1-methyl-4-nitryl-2-(trifluoromethyl) benzene to react under the action of NBS, BPO and CCl4 s
5-HT7receptor modulators: Amino groups attached to biphenyl scaffold determine functional activity
Kim, Youngjae,Park, Hyeri,Lee, Jeongeun,Tae, Jinsung,Kim, Hak Joong,Min, Sun-Joon,Rhim, Hyewhon,Choo, Hyunah
, p. 180 - 190 (2016/08/02)
5-HT7receptor (5-HT7R) agonists and antagonists have been reported to be used for treatment of neuropathic pain and depression, respectively. In this study, as a novel scaffold for 5-HT7R modulators, we designed and prepared a series of biphenyl-3-yl-methanamine derivatives with various amino groups. Evaluation of functional activities as well as binding affinities of the title compounds identified partial agonists (EC50?=?0.55–3.2?μM) and full antagonists (IC50?=?5.57–23.1?μM) depending on the amino substituents. Molecular docking study suggested that the ligand-based switch in functional activity from agonist to antagonist results from the size of the amino groups and thereby different binding modes to 5-HT7R. In particular, interaction of the ligand with Arg367 of 5-HT7R is shown to differentiate agonists and antagonists. In the pharmacophore model study, two distinct pharmacophore models can tell whether a ligand is an agonist or an antagonist. Taken together, this study provides valuable information for designing novel compounds with selective agonistic or antagonistic properties against 5-HT7R.
Synthesis and structure-activity relationships of a novel series of 2,3,5,6,7,9-hexahydrothieno[3,2-b]quinoline-8(4H)-one 1,1-dioxide K ATP channel openers: Discovery of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b] quinolin-8(4H)-one 1,1-dioxide (A-278637), a potent KATP opener that selectively inhibits spontaneous bladder contractions
Carroll, William A.,Altenbach, Robert J.,Bai, Hao,Brioni, Jorge D.,Brune, Michael E.,Buckner, Steven A.,Cassidy, Christopher,Chen, Yiyuan,Coghlan, Michael J.,Daza, Anthony V.,Drizin, Irene,Fey, Thomas A.,Fitzgerald, Michael,Gopalakrishnan, Murali,Gregg, Robert J.,Henry, Rodger F.,Holladay, Mark W.,King, Linda L.,Kort, Michael E.,Kym, Philip R.,Milicic, Ivan,Tang, Rui,Turner, Sean C.,Whiteaker, Kristi L.,Yi, Lin,Zhang, Henry,Sullivan, James P.
, p. 3163 - 3179 (2007/10/03)
Structure-activity relationships were investigated on a novel series of sulfonyldihydropyridine-containing KATP openers. Ring sizes, absolute stereochemistry, and aromatic substitution were evaluated for K ATP activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a select group of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation. In an anesthetized pig model of myogenic bladder overactivity, compound 14 and (-)-cromakalim 1 were found to inhibit spontaneous bladder contractions in vivo at plasma concentrations lower than those that affected hemodynamic parameters. Compound 14 showed approximately 5-fold greater selectivity than 1 in vivo and supports the concept that bladder-selective KATP channel openers may have utility in the treatment of overactive bladder.
