Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: Application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer

Journal of Medicinal Chemistry

Volumn 54, Issue 23, 2011, Pages 8000-8012

  Mitch, Charles H ^a   Quimby, Steven J ^a   Diaz, Nuria ^b   Pedregal, Concepcion ^b   De La Torre, Marta G ^b   Jimenez, Alma ^b   Shi, Qing ^a   Canada, Emily J ^a   Kahl, Steven D ^a   Statnick, Michael A ^a   McKinzie, David L ^a   Benesh, Dana R ^a   Rash, Karen S ^a   Barth, Vanessa N ^a  

^a ELI LILLY AND COMPANY   (United States)

^b ELI LILLY AND COMPANY   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

3 CHLORO 4 [4 [[2 (PYRIDINE 3 YL)PYRROLIDIN 1 YL]METHYL]PHENOXY]BENZAMIDE; 3 FLUORO 4 [4 [[2 (3 FLUOROPHENYL)PYRROLIDIN 1 YL]METHYL]PHENOXY]BENZAMIDE; 4 [4 [[2 (3,5 DIMETHYLPHENYL)PYRROLIDIN 1 YL]METHYL]PHENOXY] 3 FLUOROBENZAMIDE; DELTA OPIATE RECEPTOR; GUANOSINE 5' O (3 THIOTRIPHOSPHATE); KAPPA OPIATE RECEPTOR ANTAGONIST; MU OPIATE RECEPTOR; NALTREXONE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CELL STRAIN HEK293; CHO CELL; CONTROLLED STUDY; DOSE RESPONSE; DRUG ANTAGONISM; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG UPTAKE; FEMALE; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; MOLECULAR CLONING; NONHUMAN; RECEPTOR BINDING; RECEPTOR OCCUPANCY; TANDEM MASS SPECTROMETRY;

ANIMALS; BENZAMIDES; BRAIN; CHO CELLS; CHROMATOGRAPHY, LIQUID; CRICETINAE; CRICETULUS; HEK293 CELLS; HUMANS; PYRROLIDINES; RADIOLIGAND ASSAY; RATS; RECEPTORS, OPIOID, KAPPA; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TANDEM MASS SPECTROMETRY;

EID: 82555187413     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm200789r     Document Type: Article

References (41)

1. Martin, W. R.; Eades, C. G.; Thompson, J. A.; Huppler, R. E.; Gilbert, P. E. The Effects of Morphine- and Nalorphine- Like Drugs in the Nondependent and Morphine-Dependent Chronic Spinal Dog J. Pharmacol. Exp. Ther. 1976, 197, 517-532
2. Chavkin, C.; James, I. F.; Goldstein, A. Dynorphin Is a Specific Endogenous Ligand of the Kappa Opioid Receptor Science 1982, 215, 413-415
3. Schwarzer, C. 30 Years of Dynorphins-New Insights on Their Functions in Neuropsychiatric Diseases Pharmacol. Ther. 2009, 123, 353-370
4. Szmuskovicz, J.; Von Voigtlander, P. F. Benzeneacetamide Amines: Structurally Novel Non-Mu Opioids J. Med. Chem. 1982, 25, 1125-1126
5. Pfeifer, A.; Brantl, V.; Herz, A.; Emrich, H. M. Psychotomimesis Mediated by κ Opiate Receptors Science 1986, 233, 774-776
6. Spanagel, R.; Herz, A.; Shippenberg, T. S. The Effects of Opioid Peptides on Dopamine Release in the Nucleus Accumbens: an in Vivo Microdialysis Study J. Neurochem. 1990, 55, 1734-1740
7. Yasuda, K.; Raynor, K.; Kong, H.; Breder, C. D.; Takeda, J.; Reisine, T.; Bell, G. I. Cloning and Functional Comparison of Kappa and Delta Opioid Receptors from Mouse Brain Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 6736-6740
8. Mansson, E.; Bare, L.; Yang, D. Isolation of a Human Kappa Opioid Receptor cDNA from Placenta Biochem. Biophys. Res. Commun. 1994, 202, 1431-1437
9. Chen, Y.; Mestek, A.; Liu, J.; Yu, L. Molecular Cloning of a Rat Kappa Opioid Receptor Reveals Sequence Similarities to the Mu and Delta Opioid Receptors Biochem. J. 1993, 295, 625-628
10. Filizola, M.; Carteni-Farina, M.; Perez, J. J. Molecular Modeling Study of the Differential Ligand-Receptor Interaction at the Mu, Delta and Kappa Receptors J. Comput.-Aided Mol. Des. 1999, 13, 397-407
11. Metcalf, M. D.; Coop, A. Kappa Opioid Antagonists: Past Successes and Future Prospects AAPS J. 2005, 7, E704-E722
12. Nutt, D.; Groves, S.; Coupland, N.; Glue, P. Buprenorphine in Psychiatric Disorders. In Buprenorphine: Combatting Drug Abuse with a Unique Opioid; Cowan, A.; Lewis, J. W., Eds.; Wiley-Liss, Inc.; New York, 1995; pp 175-186.
13. Mague, S. D.; Pliakas, A. M.; Todtenkopf, M. S.; Tomasiewicz, H. C.; Zhang, Y.; Stevens, W. C.; Jones, R. M.; Portoghese, P. S.; Carlezon, W. A. Antidepressant-Like Effects of Kappa Opioid Receptor Antgonists in the Forced Swim Test in Rats J. Pharmacol. Exp. Ther. 2003, 305, 323-330
14. Kuzmin, A. V.; Gerrrits, A. F. M.; Van Ree, J. M. Kappa-Opioid Receptor Blockade with nor-Binaltorphimine Modulates Cocaine Self-Administration in Drug-Naïve Rats Eur. J. Pharmacol. 1998, 358, 197-202
15. Portoghese, P. S.; Lipkowski, A. W.; Takemori, A. E. Bimorphinans as Highly Selective, Potent Kappa Opioid Receptor Antagonists J. Med. Chem. 1987, 30, 238-239
16. Takemori, A. E.; Ho, B. Y.; Naeseth, J. S.; Portoghese, P. S. nor-Binaltorphimine, a Highly Selective Kappa-Opioid Antagonist in Analgesic and Receptor Binding Assays J. Pharmacol. Exp. Ther. 1988, 246, 255-258
17. Thomas, J. B.; Atkinson, R. N.; Vinson, N. A.; Catanzaro, J. L.; Perretta, C. L.; Fix, S. E.; Mascarella, S. W.; Rothman, R. B.; Xu, H.; Dersch, C.; Cantrell, B. E.; Zimmerman, D. M.; Carroll, F. I. Identification of (3 R)-7-Hydroxy- N -((1 S)-1-{[3 R,4 R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1- piperidinyl]methyl}-2-methylpropyl)1,2,3,4-tetrahydro-3-isoquinolinecarboxamide as a Novel Potent and Selective Opioid Kappa Receptor Antagonist J. Med. Chem. 2003, 46, 3127-3137
18. Brugel, T. A.; Smith, R. W.; Balestra, M.; Becker, C.; Daniels, T.; Hoerter, T. N.; Koether, G. M.; Throner, S. R.; Panko, L. M.; Folmer, J. J.; Cacciola, J.; Hunter, A. M.; Liu, R.; Edwards, P. D.; Brown, D. G.; Gordon, J.; Ledonne, N. C.; Pietras, M.; Schroeder, P.; Sygowski, L. A.; Hirata, L. T.; Zacco, A.; Peters, M. F. Discovery of 8-Azabicyclo[3.2.1]octan-3-yloxy- benzamides as Selective Antagonists of the Kappa Opioid Receptor. Part 1 Bioorg. Med. Chem. Lett. 2010, 20, 5847-5852
19. Brugel, T. A.; Smith, R. W.; Balestra, M.; Becker, C.; Daniels, T.; Koether, G. M.; Throner, S. R.; Panko, L. M.; Brown, D. G.; Liu, R.; Gordon, J.; Peters, M. F. SAR Development of a Series of 8-azabicyclo[3.2.1]octan-3-yloxy- benzamides as Kappa Opioid Receptor Antagonists. Part 2 Bioorg. Med. Chem. Lett. 2010, 20, 5405-5410
20. 11C-GR103545, a Radiotracer for Imaging Kappa-Opioid Receptors in Vivo with PET: Synthesis and Evaluation in Baboons J. Nucl. Med. 2005, 46, 484-494
21. Takeuchi, K.; Holloway, W. G.; McKinzie, J. H.; Suter, T. M.; Statnick, M. A.; Surface, P. L.; Emmerson, P. J.; Thomas, E. M.; Siegel, M. G.; Matt, J. E.; Wolfe, C. N.; Mitch, C. H. Structure-activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 1 Bioorg. Med. Chem. Lett. 2007, 17, 5349-5352
22. Takeuchi, K.; Holloway, W. G.; Mitch, C. H.; Quimby, S. J.; McKinzie, J. H.; Suter, T. M.; Statnick, M. A.; Surface, P. L.; Emmerson, P. J.; Thomas, E. M.; Siegel, M. G. Structure-activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 2 Bioorg. Med. Chem. Lett. 2007, 17, 6841-6846
23. Vidal, P.; Pedregal, C.; Diaz, N.; Broughton, H.; Acena, J. L.; Jimenez, A.; Espinosa, J. F. Assignment of Absolute Configuration on the Basis of the Conformational Effects Induced by Chiral Derivatizing Agents: The 2-Arylpyrrolidine Case Org. Lett. 2007, 9, 4123-4126
24. Stephens, P. J.; Devlin, F. J.; Pan, J. J. The Determination of the Absolute Configurations of Chiral Molecules Using Vibrational Circular Dichroism (VCD) Spectroscopy Chirality 2008, 20, 643-663
25. Seeman, J. I.; Chavdarian, C. G.; Secor, H. V. Synthesis of the Enantiomers of Nornicotine J. Org. Chem. 1985, 50, 5419-5421
26. + Modulation, Inverse Agonism, and Anorectic Potency of 4-Phenylpiperidine Opioid Antagonists Eur. J. Pharmacol. 2004, 494, 121-130
27. Rodgers, G.; Hubert, C.; McKinzie, J.; Suter, T.; Statnick, M.; Emmerson, P.; Stancato, L. Development of Displacement Binding and GTP-gamma-S Scintillation Proximity Assays for the Identification of Antagonists of the Mu Opioid Receptor Assay Drug Dev. Technol. 2003, 1, 627-636
28. Shannon, H. E.; Lutz, E. A. Comparison of the Central and Peripheral Effects of the Opioid Agonists Loperamide and Morphine in the Formalin Test in Rats Neuropharmacology 2002, 42, 253-261
29. Chernet, E.; Martin, L. J.; Li, D.; Need, A. B.; Barth, V. N.; Rash, K. S.; Phebus, L. A. Use of LC/MS to Assess Brain Tracer Distribution in Preclinical, in Vivo Receptor Occupancy Studies: Dopamine D2, Serotonin 2A and NK-1 Receptors as Examples Life Sci. 2005, 78, 340-346
30. Need, A. B.; McKinzie, J. H.; Mitch, C. H.; Statnick, M. A.; Phebus, L. A. In Vivo Rat Brain Opioid Receptor Binding of LY255582 Assessed with a Novel Method Using LC/MS/MS and the Administration of Three Tracers Simultaneously Life Sci. 2007, 81, 1389-1396
31. Akil, H.; Meng, F.; Thompson, R.; Mansour, A.; Xie, G. X.; Watson, S. J. Molecular Studies of Multiple Opioid Receptors: Cloning, Anatomical Distribution, Pharmacological Profile Regul. Pept. 1994, Suppl. 1) S9-S10
32. Mansour, A.; Fox, C. A.; Burke, S.; Watson, S. J. Immunohistochemical Localization of the Kappa1 Opioid Receptors Regul. Pept. 1994, 54, 177-178
33. Mansour, A.; Fox, C. A.; Burke, S.; Watson, S. J. Immunohistochemical Localization of the Mu Opioid Receptors Regul. Pept. 1994, 54, 179-180
34. 2 Receptor Occupancy Predicts Catalepsy and the Suppression of Conditioned Avoidance Response Behavior in Rats Pyschopharmacology 2000, 150, 422-429
35. Tempel, A.; Zukin, R. S. Neuroanatomical Patterns of the Mu, Delta and Kappa Opioid Receptors of Rat Brain as Determined by Quantitative in Vitro Autoradiography Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 4308-4312
36. Bruchas, M. R.; Yang, T.; Schreiber, S.; DeFino, M.; Kwan, S. C.; Li, S.; Chavkin, C. Long-Acting Kappa Opioid Antagonists Disrupt Receptor Signaling and Produce Noncompetitive Effects by Activating c-Jun N-terminal Kinase J. Biol. Chem. 2007, 282, 29803-29811
37. Waterhouse, R. N. Determination of Lipophilicity and Its Use as a Predictor of Blood-Brain Barrier Penetration of Molecular Imaging Agents Mol. Imaging Biol. 2003, 5, 376-389
38. Raub, T. J.; Lutzke, B. S.; Andrus, P. K.; Sawada, G. A.; Staton, B. A. Early Preclinical Evaluation of Brain Exposure in Support of Hit Identification and Lead Optimization. In: Optimizing the "Drug-Like" Properties of Leads in Discovery, Biotechnology: Pharmaceutical Aspects Series; Borchardt, R. T.; Kerns, E. H.; Hageman, M. J.; Thakker, D. R.; Stevens, J. L., Eds.; Springer: New York, 2006; pp 355-410.
39. Breiman, L. Bagging Predictors Machine Learn. 1996, 24, 123-140
40. Ivanciuc, O. Applications of Support Vector Machines in Chemistry. In: Reviews in Computational Chemistry; Lipkowitz, K. B.; Cundari, T. R., Eds.; Wiley-VCH: Weinheim, Germany, 2007, pp 291-400.
41. ten Hoeve, W.; Wynberg, H. Direct Amidoalkylation of Ketones Synth. Commun. 1994, 24, 899-906