Reid P.R.,Vanderbilt Institute of Chemical Biology Chemical Synthesis Core |
Bridges T.M.,Vanderbilt University |
Bridges T.M.,Vanderbilt Specialized Chemistry Center |
Sheffler D.J.,Vanderbilt University |
And 20 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2011
This Letter describes a chemical lead optimization campaign directed at VU0108370, a weak M1 PAM hit with a novel chemical scaffold from a functional HTS screen within the MLPCN. An iterative parallel synthesis approach rapidly established SAR for this series and afforded VU0405652 (ML169), a potent, selective and brain penetrant M1 PAM with an in vitro profile comparable to the prototypical M1 PAM, BQCA, but with an improved brain to plasma ratio. © 2010 Elsevier Ltd. All rights reserved. Source