Synthesis and characterization of a peripherally restricted CB1 cannabinoid antagonist, URB447, that reduces feeding and body-weight gain in mice

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 3, 2009, Pages 639-643

  LoVerme, Jesse ^a   Duranti, Andrea ^b   Tontini, Andrea ^b   Spadoni, Gilberto ^b   Mor, Marco ^c   Rivara, Silvia ^c   Stella, Nephi ^d   Xu, Cong ^d   Tarzia, Giorgio ^b   Piomelli, Daniele ^a,e  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF URBINO   (Italy)

^c UNIVERSITY OF PARMA   (Italy)

^d UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^e ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

Author keywords

Anti obesity agents; Peripheral cannabinoid antagonism; Pyrrolic CB antagonists; URB447

Indexed keywords

[4 AMINO 1 (4 CHLOROBENZYL) 2 METHYL 5 PHENYL 1H PYRROL 3 YL](PHENYL)METHANONE; CANNABINOID; CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID 2 RECEPTOR; RIMONABANT; UNCLASSIFIED DRUG; URB 447;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MEGADOSE; DRUG RECEPTOR BINDING; DRUG TISSUE LEVEL; FEEDING; FOOD INTAKE; HUMAN; HUMAN CELL; IC 50; LOW DRUG DOSE; MALE; MOUSE; NONHUMAN; OBESITY; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION; WEIGHT GAIN;

ANIMALS; ANTI-OBESITY AGENTS; BENZYL COMPOUNDS; BODY WEIGHT; CANNABINOIDS; CEREBELLUM; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; FEEDING BEHAVIOR; HUMANS; INHIBITORY CONCENTRATION 50; MICE; MODELS, CHEMICAL; PYRROLES; RATS; RECEPTORS, CANNABINOID; WEIGHT GAIN;

MUS; RODENTIA;

EID: 58849116267     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.12.059     Document Type: Article

References (28)

1. A provisional patent application of the subject of this publication was filed in 2007 by University of California, Irvine.
2. Cota D., Marsicano G., Lutz B., Vicennati V., Stalla G.K., Pasquali R., and Pagotto U. Int. J. Obes. Relat. Metab. Disord. 27 (2003) 289
3. Williams C.M., and Kirkham T.C. Pharmacol. Biochem. Behav. 71 (2002) 341
4. Aronne L.J., and Isoldi K.K. Am. J. Cardiol. 100 (2007) 18P
5. Kirkham T.C. Behav. Pharmacol. 16 (2005) 297
6. Storr M.A., and Sharkey K.A. Curr. Opin. Pharmacol. 7 (2007) 575
7. Pagotto U., Cervino C., Vicennati V., Marsicano G., Lutz B., and Pasquali R. Int. J. Obes. 30 Suppl. 1s (2006) S39
8. Gómez R., Navarro M., Ferrer B., Trigo J.M., Bilbao A., Del Arco I., Cippitelli A., Nava F., Piomelli D., and Rodríguez de Fonseca F. J. Neurosci. 22 (2002) 9612
9. Coutts A.A., Irving A.J., Mackie K., Pertwee R.G., and Anavi-Goffer S. J. Comp. Neurol. 448 (2002) 410
10. Burdyga G., Lal S., Varro A., Dimaline R., Thompson D.G., and Dockray G.J. J. Neurosci. 24 (2004) 2708
11. Jagerovic N., Fernandez-Fernandez C., and Goya P. Curr. Top. Med. Chem. 8 (2008) 205
12. Pavon F.J., Bilbao A., Hernández-Folgado L., Cippitelli A., Jagerovic N., Abellán G., Rodríguez-Franco M.I., Serrano A., Macias M., Gómez R., Navarro M., Goya P., and Rodríguez de Fonseca F. Neuropharmacology 51 (2006) 358
13. Chen R.Z., Frassetto A., Lao J.Z., Huang R.-R.C., Xiao J.C., Clements M.J., Walsh T.F., Hale J.J., Wang J., Tong X., and Fong T.M. Eur. J. Pharmacol. 584 (2008) 338
14. Tarzia G., Duranti A., Tontini A., Spadoni G., Mor M., Rivara S., Plazzi P.V., Kathuria S., and Piomelli D. Bioorg. Med. Chem. 11 (2003) 3965
15. Aoyagi Y., Mizusaki T., and Ohta A. Tetrahedron Lett. 37 (1996) 9203
16. Tarzia G., and Panzone G. Ann. Chim. 64 (1974) 807
17. 2O (400.90): C, 73.84; H, 5.48; N, 6.62. Found: C, 74.03; H, 5.21; N, 6.90.
18. Sprio V., and Petruso S. Ann. Chim. 63 (1973) 245
19. Petitet F., Jeanntaud B., Capet M., and Doble A. Biochem. Pharmacol. 54 (1997) 1267
20. Rinaldi-Carmona M., Barth F., Héaulme M., Shire D., Calandra B., Congy C., Martinez S., Maruani J., Néliat G., Caput D., Ferrara P., Soubrié P., Brelière J.C., and Le Fur G. FEBS Lett. 350 (1994) 240
21. Govaerts S.J., Hermans E., and Lambert D.M. Eur. J. Pharm. Sci. 23 (2004) 233
22. Calignano A., La Rana G., Giuffrida A., and Piomelli D. Nature 394 (1998) 277
23. Gleeson M.P. J. Med. Chem. 51 (2008) 817
24. LogP and PSA values were calculated by ACD/Labs 8.0, Advanced Chemistry Development Inc., Toronto, Canada.
25. Loescher W., and Potscha H. NeuroRx 2 (2005) 86
26. Meyer R.P., Gelhaus M., Knoth R., and Volk B. Curr. Drug Metab. 8 (2007) 297
27. Bermudez-Silva F.J., Sanchez-Vera I., Suárez J., Serrano A., Fuentes E., Juan-Pico P., Nadal A., and Rodríguez de Fonseca F. Eur. J. Pharmacol. 565 (2007) 207
28. Lotersztajn S., Texeira-Clerc F., Julien B., Deveaux V., Ichigotani Y., Manin S., Tran-Van-Nhieu J., Karsak M., Zimmer A., and Mallat A. Br. J. Pharmacol. 153 (2008) 286