Synthesis and evaluation of metabotropic glutamate receptor subtype 5 antagonists based on fenobam
In an effort to discover potent and selective metabotropic glutamate receptor subtype 5 (mGluR5) antagonists, 15 tetrahydropyrimidinone analogues of 1-(3-chlorophenyl)-3-(1-methyl-4-oxo-4,5-dihydro-1H-imidazol-2-yl)-urea (fenobam) were synthesized. These compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro efficacy assay. The IC50 value for 1-(3-chlorophenyl)-3-(1-methyl-4-oxo-1,4,5,6-tetrahydropyridine)urea (4g) was essentially identical to that of fenobam.
Gichinga, M., Olson, J., Butala, E., Navarro, H., Gilmour, B., Mascarella, S., & Carroll, F. (2011). Synthesis and evaluation of metabotropic glutamate receptor subtype 5 antagonists based on fenobam. ACS Medicinal Chemistry Letters, 2(12), 882-884. DOI: 10.1021/ml200162f