323591-16-8Relevant academic research and scientific papers
Structure-activity studies of novel cyanoguanidine ATP-sensitive potassium channel openers for the treatment of overactive bladder
Perez-Medrano, Arturo,Brune, Michael E.,Buckner, Steven A.,Coghlan, Michael J.,Fey, Thomas A.,Gopalakrishnan, Murali,Gregg, Robert J.,Kort, Michael E.,Scott, Victoria E.,Sullivan, James P.,Whiteaker, Kristi L.,Carroll, William A.
, p. 6265 - 6273 (2008/04/05)
A series of novel cyanoguanidine derivatives was designed and synthesized. Condensation of N-(1-benzotriazol-1-yl-2,2-dichloropropyl)-substituted benzamides with N-(substituted-pyridin-3-yl)-N′-cyanoguanidines furnished N-{2,2-dichloro-1-[N′-(substituted-pyridin-3-yl)-N′-cyanoguanidino] propyl}-substituted benzamide derivatives. These agents were glyburide-reversible potassium channel openers and hyperpolarized human bladder cells as assessed by the FLIPR membrane potential dye (KATP-FMP). These compounds were also potent full agonists in relaxing electrically stimulated pig bladder strips, an in vitro model of overactive bladder. The most active compound 9 was evaluated for in vivo efficacy and selectivity in a pig model of bladder instability. Preliminary pharmacokinetic studies in dog demonstrated excellent oral bioavailability and a t1/2 of 15 h. The synthesis, SAR studies, and biological properties of these agents are discussed.
Design and synthesis of novel cyanoguanidine ATP-sensitive potassium channel openers for the treatment of overactive bladder
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.
, p. 397 - 400 (2007/10/03)
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 KATP 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.
Potassium channel openers
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, (2008/06/13)
Compounds of formula I: are useful in treating diseases prevented by or ameliorated with potassium channel openers. Also disclosed are potassium channel opening compositions and a method of opening potassium channels in a mammal.
Potassium channel openers
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, (2008/06/13)
Compounds of formula I: are useful in treating diseases prevented by or ameliorated with potassium channel openers. Also disclosed are potassium channel opening compositions and a method of opening potassium channels in a mammal.
Aminal Diones as potassium channel openers
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, (2008/06/13)
Compounds of formula (I) 1may be useful in treating diseases prevented by or ameliorated with potassium channel openers. Also disclosed are potassium channel opening compositions and a method of opening potassium channels in a mammal.
