Design of a potent CB1 receptor antagonist series: Potential scaffold for peripherally-targeted agents

ACS Medicinal Chemistry Letters

Volumn 3, Issue 5, 2012, Pages 397-401

  Dow, Robert L ^a   Carpino, Philip A ^a   Gautreau, Denise ^a   Hadcock, John R ^a   Iredale, Philip A ^a   Kelly Sullivan, Dawn ^a   Lizano, Jeffrey S ^a   O'Connor, Rebecca E ^a   Schneider, Steven R ^a   Scott, Dennis O ^a   Ward, Karen M ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID 2 RECEPTOR; OXADIAZOLE DERIVATIVE; PF 0514273; RIMONABANT; UNCLASSIFIED DRUG;

ACETYLATION; ALKYLATION; ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLIZATION; DRUG ACTIVITY; DRUG DESIGN; DRUG EFFECT; DRUG STRUCTURE; ENANTIOMER; FOOD INTAKE; HUMAN; HUMAN CELL; LIVER MICROSOME; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

EID: 84861088535     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml3000325     Document Type: Article

References (24)

1. Flegal, K. M.; Carroll, M. D.; Ogden, C. L.; Curtin, L. R. Prevalence and trends in obesity among US adults J. Am. Med. Assoc. 2010, 303, 235-241
2. Malnick, S. D. H.; Knobler, H. The medical complications of obesity Q. J. Med. 2006, 99, 565-579 (Pubitemid 44540533)
3. Jia, H.; Lubetkin, E. I. Trends in quality-adjusted life-years lost contributed by smoking and obesity Am. J. Prev. Med. 2010, 38, 138-144
4. Pagotto, U.; Marsicano, G.; Cota, D.; Lutz, B.; Pasquali, R. The emerging role of the endocannabinoid system in endocrine regulation and energy balance Endocrine Rev. 2006, 27, 73-100 (Pubitemid 43228239)
5. Akbas, F.; Gasteyger, C.; Sjodin, A.; Astrup, A.; Larsen, T. M. A critical review of the cannabinoid receptor as a drug target for obesity management Obesity Rev. 2009, 10, 58-67
6. Howlett, A. C.; Barth, F.; Bonner, T. I.; Cabral, G.; Casellas, P.; Devane, W. A.; Felder, C. C.; Herkenham, M.; Mackie, K.; Martin, B. R.; Mechoulam, R.; Pertwee, R. G. International union of pharmacology. XXVII. Classification of cannabinoid receptors Pharmacol. Rev. 2002, 54, 161-202 (Pubitemid 34575709)
7. Sam, A. H.; Salem, V.; Ghatei, M. A.; Rimonabant: from RIO to ban. J. Obesity, 2011, Article ID 432607, DOI: 10.1155/2011/432607.
8. Aronne, L. J.; Finer, N.; Hollander, P. A.; England, R. D.; Klioze, S. S.; Chew, R. D.; Fountaine, R. J.; Powell, C. M.; Obourn, J. D. Efficacy and safety of CP-945,598, a selective cannabinoid CB1 receptor antagonist, on weight loss and maintenance Obesity 2011, 19, 1404-1414
9. Lazary, J.; Juhasz, G.; Hunyady, L.; Bagdy, G. Personalized medicine can pave the way for the safe use of CB1 receptor antagonists Trends Pharmacol. Sci. 2011, 32, 270-280
10. Engeli, S.; Bohnke, J.; Feldpausch, M.; Gorzelniak, K.; Janke, J.; Batkai, S.; Pacher, P.; Harvey-White, J.; Luft, F. C.; Sharma, A. M.; Jordan, J. Activation of the peripheral endocannabinoid system in human obesity Diabetes 2005, 54, 2838-2843 (Pubitemid 41401077)
11. 1 receptor blockade in the treatment of visceral obesity and its cardiometabolic complications Br. J. Pharmacol. 2011, 163, 1423-1431
12. Hortala, L.; Rinaldi-Carmona, M.; Congy, C.; Boulu, L.; Sadoun, F.; Fabre, G.; Finance, O.; Barth, F. Rational design of a novel peripherally-restricted, orally active CB1 cannabinoid antagonist containing a 2,3-diarylpyrrole motif Bioorg. Med. Chem. Lett. 2010, 20, 4573-4577
13. Wu, Y.-K.; Yeh, C.-F.; Ly, T. W.; Hung, M.-S. A new perspective of cannabinoid 1 receptor antagonists: approaches toward peripheral CB1R blockers without crossing the blood-brain barrier Curr. Top. Med. Chem. 2011, 11, 1421-1429
14. Fulp., A.; Bortoff, K.; Zhang, Y.; Seltzman, H.; Snyder, R.; Maitra, R. Towards rational design of cannabinoid receptor 1 (CB1) antagonists for peripheral selectivity Bioorg. Med. Chem. Lett. 2011, 21, 5711-5714
15. Tam, J.; Vemuri, V. K.; Liu, J.; Batkai, S.; Mukhopadhyay, B.; Godlewski, G.; Osei-Hyiaman, D.; Ohnuma, S.; Ambudkar, S. V.; Pickel, J.; Makriyannis, A.; Kunos, G. Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity J. Clin. Invest. 2010, 120, 2953-2966
16. Dow, R. L.; Carpino, P. A.; Hadcock, J. R.; Black, S. C.; Iredale, P. A.; DaSilva-Jardine, P.; Schneider, S. R.; Paight, E. S.; Griffith, D. A.; Scott, D. O.; O'Connor, R. E.; Nduaka, C. I. Discovery of 2-(2-chlorophenyl)-3-(4- chlorophenyl)-7-(2,2-difluoropropyl)-6,7-dihydro-2H-pyrazolo[3,4-f][1,4] oxazepin-8-(5H)-one (PF-514273), a novel, bicyclic lactam-based cannabinoid-1 receptor antagonist for the treatment of obesity J. Med. Chem. 2009, 52, 2652-2655
17. Hanus, L. O.; Mechoulam, R. Novel natural and synthetic ligands of the endocannabinoid system Curr. Med. Chem. 2010, 17, 1341-1359
18. Shim, J.-Y.; Welsh, W. J.; Cartier, E.; Edwards, J. L.; Howlett, A. C. Molecular interaction of the antagonist N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide with the CB1 cannabinoid receptor J. Med. Chem. 2002, 45, 1447-1459 (Pubitemid 34246108)
19. Leeson, P. D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry Nat. Rev. Drug Discovery 2007, 6, 881-890 (Pubitemid 350042396)
20. Obach, R. S. Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: an examination of in vitro half-life approach and nonspecific binding to microsomes Drug Metab. Dispos. 1999, 27, 1350-1359
21. Little, P. J.; Compton, D. R.; Johnson, M. R.; Melvin, L. S.; Martin, B. R. Pharmacology and stereoselectivity of structurally novel cannabinoids in mice J. Pharmacol. Exp. Ther. 1988, 247, 1046-1051 (Pubitemid 19022114)
22. Troutman, M. D.; Luo, G.; Gan, L. S.; Thakker, D. R. The role of p-glycoprotein in drug disposition: significance to drug development. In Drug-Drug Interactions; Rodrigues, A. D., Ed.; Marcel Dekker: New York, pp 295-357.
23. Feng, B.; Mills, J. B.; Davidson, R. E.; Mireles, R. J.; Janiszewski, J. S.; Troutman, M. D.; de Morais, S. M. In vitro p-glycoprotein assays to predict the in vivo interactions of p-glycoprotein with drugs in the central nervous system Drug Metab. Dispos. 2008, 36, 268-275 (Pubitemid 351185738)
24. Wager, T. T.; Chandrasekaran, R. Y.; Hou, X.; Troutman, M. D.; Verhoest, P. R.; Villalobos, A.; Will, Y. Defining desirable central nervous system drug space through the alignment of molecular properties, in vitro ADME and safety attributes ACS Chem. Neurosci. 2010, 1, 420-434