Chemical lead optimization of a pan G sub(q) mAChR M sub(1), M sub(3), M sub(5) positive allosteric modulator (PAM) lead. Part II: Development of a potent and highly selective M sub(1) PAM

Chemical lead optimization of a pan G sub(q) mAChR M sub(1), M sub(3), M sub(5) positive allosteric modulator (PAM) lead. Part II: Development of a potent and highly selective M sub(1) PAM

This Letter describes a chemical lead optimization campaign directed at VU0119498, a pan G sub(q) mAChR M sub(1), M sub(3), M sub(5) positive allosteric modulator (PAM) with the goal of developing a selective M sub(1) PAM. An iterative library synthesis approach delivered a potent (M sub(1) EC sub(5...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2010-03, Vol.20 (6), p.1972-1975
Hauptverfasser: Bridges, Thomas M, Kennedy, JPhillip, Noetzel, Meredith J, Breininger, Micah L, Gentry, Patrick R, Conn, PJeffrey, Lindsley, Craig W
Format: Artikel
Sprache:eng
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Zusammenfassung:This Letter describes a chemical lead optimization campaign directed at VU0119498, a pan G sub(q) mAChR M sub(1), M sub(3), M sub(5) positive allosteric modulator (PAM) with the goal of developing a selective M sub(1) PAM. An iterative library synthesis approach delivered a potent (M sub(1) EC sub(50) = 830 nM) and highly selective M sub(1) PAM (>30 kM vs M sub(2)-M sub(5)). AB:
ISSN:0960-894X
DOI:10.1016/j.bmcl.2010.01.109