Design and synthesis of novel cyanoguanidine ATP-sensitive potassium channel openers for the treatment of overactive bladder

Arturo Perez-Medrano; Steven A Buckner; Michael J Coghlan; Robert J Gregg; Murali Gopalakrishnan; Michael E Kort; John K Lynch; Victoria E Scott; James P Sullivan; Kristi L Whiteaker; William A Carroll

doi:10.1016/j.bmcl.2003.10.063

Design and synthesis of novel cyanoguanidine ATP-sensitive potassium channel openers for the treatment of overactive bladder

Bioorg Med Chem Lett. 2004 Jan 19;14(2):397-400. doi: 10.1016/j.bmcl.2003.10.063.

Authors

Arturo Perez-Medrano¹, Steven A Buckner, Michael J Coghlan, Robert J Gregg, Murali Gopalakrishnan, Michael E Kort, John K Lynch, Victoria E Scott, James P Sullivan, Kristi L Whiteaker, William A Carroll

Affiliation

¹ Abbott Laboratories, Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA. [email protected]

PMID: 14698167
DOI: 10.1016/j.bmcl.2003.10.063

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.

MeSH terms

Adenosine Triphosphate / pharmacology*
Animals
Drug Design
Guanidines / chemical synthesis*
Guanidines / pharmacology
Guanidines / therapeutic use
Humans
In Vitro Techniques
Muscle, Smooth / drug effects
Muscle, Smooth / metabolism
Potassium Channels / metabolism*
Swine
Urinary Bladder / drug effects
Urinary Bladder / metabolism
Urinary Bladder / physiology
Urinary Bladder Diseases / drug therapy*
Urinary Bladder Diseases / metabolism

Substances

Guanidines
Potassium Channels
Adenosine Triphosphate
dicyandiamido