Details

Autor(en) / Beteiligte

• Jeppesen, Lone
• Olesen, Preben H
• Hansen, Lena
• Sheardown, Malcolm J
• Thomsen, Christian
• Rasmussen, Thøger
• 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

Titel

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

Ist Teil von

• Journal of medicinal chemistry, 1999-06, Vol.42 (11), p.1999-2006

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

1999

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.