This Letter describes a chemical lead optimization campaign directed at VU0119498, a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) with the goal of developing a selective M(1) PAM. An iterative library synthesis approach delivered a potent (M(1) EC(50)=830 nM) and highly selective M(1) PAM (>30 microM vs M(2)-M(5)).
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834874 | PMC |
| http://dx.doi.org/10.1016/j.bmcl.2010.01.109 | DOI Listing |
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