Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs).
AUTHORS
Engers
DWDarren W ,
Niswender
CM Colleen M ,
Weaver
CD C David ,
Jadhav
S Satyawan ,
Menon
UN Usha N ,
Zamorano
R Rocio ,
Conn
PJ P Jeffrey ,
Lindsley
CW Craig W ,
Hopkins
CR Corey R .
Journal of medicinal chemistry. 2009 7 23; 52(14).
4115-8
- PMID: 19469556[PubMed].
- PMCID: PMC2765192.
- NIHMSID: NIHMS120162
ABSTRACT
We report the synthesis and evaluation of a series of heterobiaryl amides as positive allosteric modulators of mGluR4. Compounds 9b and 9c showed submicromolar potency at both human and rat mGluR4. In addition, both 9b and 9c were shown to be centrally penetrant in rats using nontoxic vehicles, a major advance for the mGluR4 field.
We report the synthesis and evaluation of a series of heterobiaryl amides as positive allosteric modulators of mGluR4. Compounds 9b and 9c showed submicromolar potency at both human and rat mGluR4. In addition, both 9b and 9c were shown to be centrally penetrant in rats using nontoxic vehicles, a major advance for the mGluR4 field.