215054-57-2Relevant articles and documents
1-(1,2,5-thiadiazol-4-yl)-4-azatricyclo[2.2.1.02,6]heptanes as new potent muscarinic M1 agonists: Structure-activity relationship for 3-aryl- 2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives
Jeppesen, Lone,Olesen, Preben H.,Hansen, Lena,Sheardown, Malcolm J.,Thomsen, Christian,Rasmussen, Th?ger,Jensen, Anders Fink,Christensen, Michael S.,Rimvall, Karin,Ward, John S.,Whitesitt, Celia,Calligaro, David O.,Bymaster, Frank P.,Delapp, Neil W.,Felder, Christian C.,Shannon, Harlan E.,Sauerberg, Per
, p. 1999 - 2006 (1999)
Two new series of 1-(1,2,5-thiadiazol-4-yl)-4- azatricyclo[2.2.1.02,6]heptanes were synthesized and evaluated for their in vitro activity in cell lines transfected with either the human M1 or M2 receptor. 3-Phenyl-2-propyn-1-yloxy and -1-ylthio analogues substituted with halogen in the meta position showed high functional potency, efficacy, and selectivity toward the M1 receptor subtype. A quite unique functional M1 receptor selectivity was observed for compounds 8b, 8d, 8f, 9b, 9d, and 9f. Bioavailability studies in rats indicated an oral bioavailability of about 20-30%, with the N-oxide as the only detected metabolite.
