@article{510414c683824ea6aa182511afa46171,
title = "The discovery of VU0652957 (VU2957, Valiglurax): SAR and DMPK challenges en route to an mGlu4 PAM development candidate",
abstract = "This letter describes the first account of the chemical optimization (SAR and DMPK profiling) of a new series of mGlu4 positive allosteric modulators (PAMs), leading to the identification of VU0652957 (VU2957, Valiglurax), a compound profiled as a preclinical development candidate. Here, we detail the challenges faced in allosteric modulator programs (e.g., steep SAR, as well as subtle structural changes affecting overall physiochemical/DMPK properties and CNS penetration).",
keywords = "Metabotropic glutamate receptor, Parkinson's disease (PD), Positive allosteric modulator (PAM), Structure-activity relationship (SAR), mGlu",
author = "Panarese, {Joseph D.} and Engers, {Darren W.} and Wu, {Yong Jin} and Guernon, {Jason M.} and Aspen Chun and Gregro, {Alison R.} and Bender, {Aaron M.} and Capstick, {Rory A.} and Wieting, {Joshua M.} and Bronson, {Joanne J.} and Macor, {John E.} and Ryan Westphal and Matthew Soars and Engers, {Julie E.} and Felts, {Andrew S.} and Rodriguez, {Alice L.} and Emmitte, {Kyle A.} and Jones, {Carrie K.} and Blobaum, {Anna L.} and {Jeffrey Conn}, P. and Niswender, {Colleen M.} and Hopkins, {Corey R.} and Lindsley, {Craig W.}",
note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",
year = "2019",
month = jan,
day = "15",
doi = "10.1016/j.bmcl.2018.10.050",
language = "English",
volume = "29",
pages = "342--346",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Ltd",
number = "2",
}