Discovery, synthesis, and structure-activity relationship development of a series of N-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)) with CNS exposure in rats.
AUTHORS
Engers
DWDarren W ,
Field
JR Julie R ,
Le
U Uyen ,
Zhou
Y Ya ,
Bolinger
JD Julie D ,
Zamorano
R Rocio ,
Blobaum
AL Anna L ,
Jones
CK Carrie K ,
Jadhav
S Satyawan ,
Weaver
CD C David ,
Conn
PJ P Jeffrey ,
Lindsley
CW Craig W ,
Niswender
CM Colleen M ,
Hopkins
CR Corey R .
Journal of medicinal chemistry. 2011 2 24; 54(4).
1106-10
- PMID: 21247167[PubMed].
- PMCID: PMC3166797.
- NIHMSID: NIHMS266460
ABSTRACT
Herein we report the discovery, synthesis, and evaluation of a series of N-(4-acetamido)-phenylpicolinamides as positive allosteric modulators of mGlu(4). Compounds from the series show submicromolar potency at both human and rat mGlu(4). In addition, pharmacokinetic studies utilizing subcutaneous dosing demonstrated good brain exposure in rats.
Herein we report the discovery, synthesis, and evaluation of a series of N-(4-acetamido)-phenylpicolinamides as positive allosteric modulators of mGlu(4). Compounds from the series show submicromolar potency at both human and rat mGlu(4). In addition, pharmacokinetic studies utilizing subcutaneous dosing demonstrated good brain exposure in rats.