Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators

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 parallel synthesis approach was employed to incorporate basic heterocycles to improve physiochemical properties. (C) 2010 Elsevier Ltd. All rights reserved.