Letters
Journal of Medicinal Chemistry, 2006, Vol. 49, No. 26 7587
1,8-naphthyidinones and their evaluation as novel, orally active CB1
receptor inverse agonists. Bioorg. Med. Chem. Lett. 2006, 16, 681-
685. (d) Plummer, C. W.; Finke, P. E.; Mills, S. G.; Wang, J.; Tong,
X.; Doss, G. A.; Fong, T. M.; Lao, J. Z.; Schaeffer, M.-T.; Chen, J.;
Shen, C.-P.; Stribling, D. S.; Shearman, L. P.; Strack, A. M.; Van
der Ploeg, L. H. T. Synthesis and activity of 4,5-diarylimidazoles as
human CB1 receptor inverse agonists. Bioorg. Med. Chem. Lett. 2005,
15, 1441-1446.
bioavailable. A major focus of the optimization effort was to
increase in vivo efficacy and to attenuate the potential for bioac-
tivation of the initial lead. These compounds are active in models
of feeding behavior and hypothermia, and 48 (MK-0364) is cur-
rently undergoing clinical evaluation for the treatment of obesity.
Acknowledgment. We acknowledge the contributions of Ms.
Nancy Tsou, Dr. Richard Ball, Dr. David Mathre, Ms. Dorothy
Levorse, Dr. Karen Owens, and many members of the Labora-
tory of Animal Resources.
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Supporting Information Available: Experimental details and
elemental analysis results. This material is available free of charge
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(10) The stereochemistry of 36 was confirmed by X-ray analysis. Also
see: Burns, D. H.; Chen, A. M.; Gibson, R. E.; Goulet, M. T.;
Hagmann, W. K.; Hamill, T. G.; Jewell, J. P.; Lin, L. S.; Liu, P.;
Peresypkin, A. V. Radiolabeled cannabinoid-1 receptor modulators.
PCT Patent Application WO2005/009479A1, 2005.
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(12) (a) Evans, D. C.; Watt, A. P.; Nicoll-Griffith, D. A.; Baillie, T. A.
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(13) Samuel, K.; Yin, W.; Stearns, R. A.; Tang, Y. S.; Chaudhary, A. G.;
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