Design and synthesis of novel cyanoguanidine ATP-sensitive potassium channel openers for the treatment of overactive bladder |
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| Authors: | Perez-Medrano Arturo Buckner Steven A Coghlan Michael J Gregg Robert J Gopalakrishnan Murali Kort Michael E Lynch John K Scott Victoria E Sullivan James P Whiteaker Kristi L Carroll William A |
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| Institution: | Abbott Laboratories, Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA. arturo.perezmedrano@abbott.com |
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| Abstract: | Thiourea derivatives were identified as glyburide-reversible potassium channel openers through high-throughput screening. Based on these findings, a number of novel cyanoguanidines were designed and synthesized, which hyperpolarized human bladder K(ATP) channels. These agents are potent full agonists in relaxing electrically-stimulated pig bladder strips. The synthesis, SAR and biological properties of these agents are discussed. |
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