106877-33-2Relevant articles and documents
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.
Experimental and Computational Studies of Trifluoromethylation of Aromatic Amines by the System Trifluoroiodomethane-Zinc-Sulfur Dioxide
Strekowski, Lucjan,Hojjat, Maryam,Petterson, Steven E.,Kiselyov, Alexander S.
, p. 1413 - 1416 (2007/10/02)
Several trifluoromethyl-substituted aromatic and heteroaromatic amines have been obtained by the reactions of the corresponding amines with the title reagent system.Computational results provide rationalization for the observed regioselectivities and support a mechanism in which the electrophilic trifluoromethyl radicals interact with the aromatic ring at the sites with the greatest electron density of the HOMO orbitals, and then the resultant adducts are oxidized to cations.The products obtained are potential building blocks for a number of heterocyclic systems.