title: Design and synthesis of novel cyanoguanidine ATP-sensitive potassium channel openers for the treatment of overactive bladder.
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.
authors.affiliation: Abbott Laboratories, Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA. arturo.perezmedrano@abbott.com
authors.forename: Arturo
authors.initials: A
authors.lastname: Perez-Medrano
authors.forename: Steven A
authors.initials: SA
authors.lastname: Buckner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Coghlan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gregg
authors.forename: Murali
authors.initials: M
authors.lastname: Gopalakrishnan
authors.forename: Michael E
authors.initials: ME
authors.lastname: Kort
authors.forename: John K
authors.initials: JK
authors.lastname: Lynch
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Scott
authors.forename: James P
authors.initials: JP
authors.lastname: Sullivan
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Whiteaker
authors.forename: William A
authors.initials: WA
authors.lastname: Carroll
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D015195:Drug Design; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001745:Urinary Bladder Diseases / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D006146:Guanidines; D015221:Potassium Channels; D000255:Adenosine Triphosphate; C004711:dicyandiamido