- Identification and structure–activity relationship exploration of uracil-based benzoic acid and ester derivatives as novel dipeptidyl Peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus
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Our previously reported carboxyl-containing DPP-4 inhibitors were highly potent but were poorly bioavailable. Esters of the carboxyl analogs exhibited a significant DPP-4 potency loss albeit with enhanced oral absorption. Herein, we described identificati
- Deng, Xiaoyan,Jiang, Neng,Jiang, Weizhe,Li, Qing,Meng, Liuwei,Xing, Junhao,Xu, Yanjun
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- Rational design of agonists for bitter taste receptor TAS2R14: from modeling to bench and back
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Human bitter taste receptors (TAS2Rs) are a subfamily of 25 G protein-coupled receptors that mediate bitter taste perception. TAS2R14 is the most broadly tuned bitter taste receptor, recognizing a range of chemically diverse agonists with micromolar-range potency. The receptor is expressed in several extra-oral tissues and is suggested to have physiological roles related to innate immune responses, male fertility, and cancer. Higher potency ligands are needed to investigate TAS2R14 function and to modulate it for future clinical applications. Here, a structure-based modeling approach is described for the design of TAS2R14 agonists beginning from flufenamic acid, an approved non-steroidal anti-inflammatory analgesic that activates TAS2R14 at sub-micromolar concentrations. Structure-based molecular modeling was integrated with experimental data to design new TAS2R14 agonists. Subsequent chemical synthesis and in vitro profiling resulted in new TAS2R14 agonists with improved potency compared to the lead. The integrated approach provides a validated and refined structural model of ligand–TAS2R14 interactions and a general framework for structure-based discovery in the absence of closely related experimental structures.
- Di Pizio, Antonella,Waterloo, Lukas A. W.,Brox, Regine,L?ber, Stefan,Weikert, Dorothee,Behrens, Maik,Gmeiner, Peter,Niv, Masha Y.
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p. 531 - 542
(2019/07/03)
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- Synthesis and structure-activity relationships of novel benzoxaboroles as a new class of antimalarial agents
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A series of boron-containing benzoxaborole compounds was designed and synthesized for a structure-activity relationship investigation surrounding 7-(HOOCCH2CH2)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (1) with the goal of discovering
- Zhang, Yong-Kang,Plattner, Jacob J.,Freund, Yvonne R.,Easom, Eric E.,Zhou, Yasheen,Gut, Jiri,Rosenthal, Philip J.,Waterson, David,Gamo, Francisco-Javier,Angulo-Barturen, Inigo,Ge, Min,Li, Zhiya,Li, Lingchao,Jian, Yong,Cui, Han,Wang, Hailong,Yang, Jian
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experimental part
p. 644 - 651
(2011/03/18)
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- INDAZOLONE ANALOGS AS GLYCOGEN SYNTHASE ACTIVATORS
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful
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Page/Page column 9
(2011/05/16)
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- An efficient synthesis for a new class antimalarial agent, 7-(2-carboxyethyl)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole
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Efficient synthesis is essential for antimalarial therapeutics. A four-step route has been established for the synthesis of 7-(2-carboxyethyl)-1,3-dihydro- 1-hydroxy-2,1-benzoxaborole 1 that is a potent new class boron-containing antimalarial agent in pre
- Zhang, Yong-Kang,Plattner, Jacob J.,Easom, Eric E.,Waterson, David,Ge, Min,Li, Zhiya,Li, Lingchao,Jian, Yong
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supporting information; experimental part
p. 3909 - 3911
(2011/08/09)
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- Design, synthesis and identification of novel colchicine-derived immunosuppressant
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Synthesis and biological evaluation of various colchicine analogues through the mixed-lymphocyte reaction (MLR), lymphoproliferation, and inhibitory effects on the inflammatory genes are described. In addition, a new series of immunosuppressive agents developed on the structural basis of colchicine, as well as their structure-activity relationships is reported. The most potent analogue 20a exhibited an excellent immunosuppressive activity on in vivo skin-allograft model, which is comparable to that of cyclosporin A.
- Chang, Dong-Jo,Yoon, Eun-Young,Lee, Geon-Bong,Kim, Soon-Ok,Kim, Wan-Joo,Kim, Young-Myeong,Jung, Jong-Wha,An, Hongchan,Suh, Young-Ger
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scheme or table
p. 4416 - 4420
(2010/04/05)
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- 2-SULFANYL-BENZOIMIDAZOL-1-YL-ACETIC ACID DERIVATIVES AS CRTH2 ANTAGONISTS
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The invention relates to 2-sulfanyl-benzoimidazol-1-yl-acetic acid derivatives and their use as potent "chemoattractant receptor-homologous molecule expressed on Th2 cells" antagonists in the treatment of prostaglandin mediated diseases, to pharmaceutical compositions containing these derivatives and to processes for their preparation.
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Page/Page column 98
(2010/10/20)
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