Bioorganic and Medicinal Chemistry Letters p. 2897 - 2902 (1998)
Update date:2022-08-05
Topics:
Sauerberg, Per
Jeppesen, Lone
Olesen, Preben H.
Sheardown, Malcolm J.
Fink-Jensen, Anders
Rasmussen, Thoger
Rimvall, Karin
Shannon, Harlan E.
Bymaster, Frank P.
DeLapp, Neil W.
Calligaro, Dave O.
Ward, John S.
Whitesitt, Celia A.
Thomsen, Christian
Series of analogs to the functional m1 selective agonist, xanomeline (hexyloxy-TZTP), were evaluated for their in vitro ml efficacy in cell lines transfected with the human m1 receptor. Systematic variation of the side chain and the azacyclic ring led to the discovery of potent muscarinic agonists with robust m1 efficacy, all having the phenylpropargyloxy/thio as the side chain. The most selective compound was the phenylpropargylthio- [3.2.1] endo analog 28, which is a potent and efficacious m1 agonist with no m2 activity.
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