Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM

Thomas M Bridges; J Phillip Kennedy; Hyekyung P Cho; Micah L Breininger; Patrick R Gentry; Corey R Hopkins; P Jeffrey Conn; Craig W Lindsley

doi:10.1016/j.bmcl.2009.11.089

Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM

Thomas M Bridges, J Phillip Kennedy, Hyekyung P Cho, Micah L Breininger, Patrick R Gentry, Corey R Hopkins, P Jeffrey Conn, Craig W Lindsley

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

38 Citationer (Scopus)

Abstract

This Letter describes a chemical lead optimization campaign directed at VU0238429, the first M(5)-preferring positive allosteric modulator (PAM), discovered through analog work around VU0119498, a pan G(q) mAChR M(1), M(3), M(5) PAM. An iterative library synthesis approach delivered the first selective M(5) PAM (no activity at M(1)-M(4) @ 30microM), and an important tool compound to study the role of M(5) in the CNS.

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry Letters
Vol/bind	20
Udgave nummer	2
Sider (fra-til)	558-62
Antal sider	5
ISSN	0960-894X
DOI	https://doi.org/10.1016/j.bmcl.2009.11.089
Status	Udgivet - 15 jan. 2010
Udgivet eksternt	Ja

Bibliografisk note

Adgang til dokumentet

10.1016/j.bmcl.2009.11.089

Citationsformater

Bridges, T. M., Kennedy, J. P., Cho, H. P., Breininger, M. L., Gentry, P. R., Hopkins, C. R., Conn, P. J., & Lindsley, C. W. (2010). Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM. Bioorganic & Medicinal Chemistry Letters, 20(2), 558-62. https://doi.org/10.1016/j.bmcl.2009.11.089

Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM. / Bridges, Thomas M; Kennedy, J Phillip; Cho, Hyekyung P et al.
I: Bioorganic & Medicinal Chemistry Letters, Bind 20, Nr. 2, 15.01.2010, s. 558-62.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Bridges, TM, Kennedy, JP, Cho, HP, Breininger, ML, Gentry, PR, Hopkins, CR, Conn, PJ & Lindsley, CW 2010, 'Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM', Bioorganic & Medicinal Chemistry Letters, bind 20, nr. 2, s. 558-62. https://doi.org/10.1016/j.bmcl.2009.11.089

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abstract = "This Letter describes a chemical lead optimization campaign directed at VU0238429, the first M(5)-preferring positive allosteric modulator (PAM), discovered through analog work around VU0119498, a pan G(q) mAChR M(1), M(3), M(5) PAM. An iterative library synthesis approach delivered the first selective M(5) PAM (no activity at M(1)-M(4) @ 30microM), and an important tool compound to study the role of M(5) in the CNS.",

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KW - Receptor, Muscarinic M5/agonists

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