ACS Medicinal Chemistry Letters
Letter
(13) Friedmann, C. T. H.; Davis, L. J.; Ciccone, P. E.; Rubin, R. T.
Phase II double blind controlled study of a new anxiolytic, fenobam.
Curr. Ther. Res. 1980, 27, 144−151.
This research was supported by the National Institute on Drug
Abuse, Grant DA05477.
Notes
(14) Ceccarelli, S. M.; Jaeschke, G.; Buettelmann, B.; Huwyler, J.;
Kolczewski, S.; Peters, J. U.; Prinssen, E.; Porter, R.; Spooren, W.;
Vieira, E. Rational design, synthesis, and structure-activity relationship
of benzoxazolones: New potent mglu5 receptor antagonists based on
the fenobam structure. Biorg. Med. Chem. Lett. 2007, 17, 1302−1306.
(15) Jaeschke, G.; Porter, R.; Buttelmann, B.; Ceccarelli, S. M.; Guba,
W.; Kuhn, B.; Kolczewski, S.; Huwyler, J.; Mutel, V.; Peters, J. U.;
Ballard, T.; Prinssen, E.; Vieira, E.; Wichmann, J.; Spooren, W.
Synthesis and biological evaluation of fenobam analogs as mGlu5
receptor antagonists. Bioorg. Med. Chem. Lett. 2007, 17, 1307−1311.
(16) Porter, R. H.; Jaeschke, G.; Spooren, W.; Ballard, T. M.;
Buttelmann, B.; Kolczewski, S.; Peters, J. U.; Prinssen, E.; Wichmann,
J.; Vieira, E.; Muhlemann, A.; Gatti, S.; Mutel, V.; Malherbe, P.
Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a
potent, selective, and noncompetitive mGlu5 receptor antagonist with
inverse agonist activity. J. Pharmacol. Exp. Ther. 2005, 315, 711−721.
(17) Wallberg, A.; Nilsson, K.; Osterlund, K.; Peterson, A.; Elg, S.;
Raboisson, P.; Bauer, U.; Hammerland, L. G.; Mattsson, J. P. Phenyl
ureas of creatinine as mGluR5 antagonists. A structure-activity
relationship study of fenobam analogues. Bioorg. Med. Chem. Lett.
2006, 16, 1142−1145.
Part of the research was presented at the 241st National
Meeting and Exposition of the American Chemical Society,
Anaheim, CA, March 27−31, 2011. Gichinga, M. G.; Butala, E.;
Navarro, H. A.; Gilmour, B. P.; Carroll, F. I. Synthesis and
evaluation of tetrahydropyrimidinone-based fenobam analogues
as metabotropic glutamate receptor subtype 5 antagonists.
Abstr. Pap. Am. Chem. Soc. 2011, 241.
ABBREVIATIONS
■
CHO-K1, Chinese hamster ovary; mGluR5, metabotropic
glutamate receptor 5; MPEP, 3-methyl-6-(phenylethynyl)-
pyridine; MTEP, (2-methyl-1,3-thiazol-4-yl)ethynylpyridine;
PK, pharmacokinetic; tPSA, total polar surface area; cDNA,
complementary DNA
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