@article{1a8c6761283c45859f3783aeb36c07e2,
title = " Discovery of Novel Central Nervous System Penetrant Metabotropic Glutamate Receptor Subtype 2 (mGlu 2 ) Negative Allosteric Modulators (NAMs) Based on Functionalized Pyrazolo[1,5- a]pyrimidine-5-carboxamide and Thieno[3,2- b]pyridine-5-carboxamide Cores ",
abstract = " A scaffold hopping exercise from a monocyclic mGlu 2 NAM with poor rodent PK led to two novel heterobicyclic series of mGlu 2 NAMs based on either a functionalized pyrazolo[1,5-a]pyrimidine-5-carboxamide core or a thieno[3,2-b]pyridine-5-carboxamide core. These novel analogues possess enhanced rodent PK, while also maintaining good mGlu 2 NAM potency, selectivity (versus mGlu 3 and the remaining six mGlu receptors), and high CNS penetration. Interestingly, SAR was divergent between the new 5,6-heterobicyclic systems.",
author = "Childress, {Elizabeth S.} and Wieting, {Joshua M.} and Felts, {Andrew S.} and Breiner, {Megan M.} and Long, {Madeline F.} and Luscombe, {Vincent B.} and Rodriguez, {Alice L.} and Cho, {Hyekyung P.} and Blobaum, {Anna L.} and Niswender, {Colleen M.} and Emmitte, {Kyle A.} and Conn, {P. Jeffrey} and Lindsley, {Craig W.}",
note = "Funding Information: This work was generously supported by the NIH and NIMH, grant R01 MH 099269 (K.A.E.) and grant R01 MH108498 (C.W.L). We also thank the Warren Family and Foundation for establishing the William K. Warren, Jr. Chair in Medicine (C.W.L.). Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",
year = "2019",
month = oct,
day = "1",
doi = "10.1021/acs.jmedchem.8b01266",
language = "English",
volume = "62",
pages = "378--384",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "1",
}