Biarylpyrazole inverse agonists at the cannabinoid CB1 receptor: Importance of the C-3 carboxamide oxygen/lysine3.28(192) interaction

Journal of Medicinal Chemistry

Volumn 49, Issue 20, 2006, Pages 5969-5987

  Hurst, Dow ^a   Umejiego, Uju ^a   Lynch, Diane ^a   Seltzman, Herbert ^b   Hyatt, Steven ^b   Roche, Michael ^b   McAllister, Sean ^c   Fleischer, Daniel ^c   Kapur, Ankur ^c   Abood, Mary ^c   Shi, Shanping ^d   Jones, Jannie ^d   Lewis, Deborah ^d   Reggio, Patricia ^a  

^a UNIVERSITY OF NORTH CAROLINA AT GREENSBORO   (United States)

^b RTI INTERNATIONAL   (United States)

^c CALIFORNIA PACIFIC MEDICAL CENTER   (United States)

^d MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 [5 (4 CHLOROPHENYL) 1 (2,4 DICHLOROPHENYL) 4 METHYL 1H PYRAZOLE 3 YL]VINYL]PIPERIDINE; 2,3 DIHYDRO 5 METHYL 3 (MORPHOLINOMETHYL) 6 (1 NAPHTHOYL)PYRROLO[1,2,3 DE][1,4]BENZOXAZINE; 4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; 5 (4 CHLOROPHENYL) 1 (2,4 DICHLOROPHENYL) 4 METHYL 1H PYRAZOLE 3 (N CYCLOHEXYLCARBOXAMIDE); 5 (4 CHLOROPHENYL) 1 (2,4 DICHLOROPHENYL) 4 METHYL 3 (PIPERIDINOIMINOMETHYL) 1H PYRAZOLE; 5 (4 CHLOROPHENYL) 3 (2 CYCLOHEXYLETHENYL) 1 (2,4 DICHLOROPHENYL) 4 METHYL 1H PYRAZOLE; AMIDE; CALCIUM CHANNEL; CANNABINOID 1 RECEPTOR; CANNABINOID RECEPTOR AGONIST; CANNABINOID RECEPTOR ANTAGONIST; G PROTEIN COUPLED RECEPTOR; LYSINE; NITROGEN; OXYGEN; PIPERIDINE DERIVATIVE; PYRAZOLE DERIVATIVE; RIMONABANT; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ANIMAL CELL; ARTICLE; CALCIUM CURRENT; CELL STRAIN HEK293; CONTROLLED STUDY; DRUG CONFORMATION; DRUG DESIGN; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HYDROGEN BOND; IMMUNOFLUORESCENCE; LIGAND BINDING; MOLECULAR MODEL; NONHUMAN; OLEFINATION; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; RECEPTOR AFFINITY; SUPERIOR CERVICAL GANGLION; THERMODYNAMICS; VOLTAGE CLAMP; WITTIG REACTION;

AMIDES; AMINO ACID SEQUENCE; BINDING SITES; BINDING, COMPETITIVE; CALCIUM; CELL LINE; HUMANS; LIGANDS; LYSINE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; MUTATION; NEURONS; OXYGEN; PYRAZOLES; RADIOLIGAND ASSAY; RATS; RECEPTOR, CANNABINOID, CB1; STEREOISOMERISM; SUPERIOR CERVICAL GANGLION; THERMODYNAMICS;

EID: 33749239422     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm060446b     Document Type: Article

References (54)

1. Hurst, D. P.; Lynch, D. L.; Barnett-Norris, J.; Hyatt, S. M.; Seltzman, H. H.; et al. N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlo-rophenyl)-4- methyl-H-pyrazole-3-carboxamide (SR141716A) interaction with LYS 3.28(192) is crucial for its inverse agonism at the cannabinoid CB1 receptor. Mol. Pharmacol. 2002, 62, 1274-1287.
2. Felder, C. C.; Joyce, K. E.; Briley, E. M.; Mansouri, J.; Mackie, K.; et al. Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol. Pharmacol 1995, 48, 443-450.
3. Mackie, K.; Lai, Y.; Westenbroek, R.; Mitchell, R. Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J. Neurosci. 1995, 15, 6552-6561.
4. Pan, X.; Ikeda, S. R.; Lewis, D. L. Rat brain cannabinoid receptor modulates N-type Ca2+ channels in a neuronal expression system. Mol. Pharmacol. 1996, 49, 707-714.
5. Rinaldi-Carmona, M.; Barth, F.; Heaulme, M.; Shire, D.; Calandra, B.; et al. SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett. 1994, 350, 240-244.
6. Lange, J. H.; Kruse, C. G. Keynote review: Medicinal chemistry strategies to CB1 cannabinoid receptor antagonists. Drug Discovery-Today 2005, 10, 693-702.
7. Jagerovic, N.; Hernandez-Folgado, L.; Alkorta, I.; Goya, P.; Navarro, M.; et al. Discovery of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1h-1,2,4- triazole, a novel in vivo cannabinoid antagonist containing a 1,2.4-triazole motif. J. Med. Chem. 2004, 47, 2939-2942.
8. Lange, J. H.; van Stuivenberg, H. H.; Coolen, H. K.; Adolfs, T. J.; McCreary, A. C.; et al. Bioisosteric replacements of the pyrazole moiety of rimonabant: synthesis, biological properties, and molecular modeling investigations of thiazoles, triazoles, and imidazoles as potent and selective CB1 cannabinoid receptor antagonists. J. Med. Chem. 2005, 48, 1823-1838.
9. Lange, J. H.; Coolen, H. K.; van Stuivenberg, H. H.; Dijksman, J. A.; Herremans, A. H.; et al. Synthesis, biological properties, and molecular modeling investigations of novel 3,4-diarylpyrazolines as potent and selective CB(1) cannabinoid receptor antagonists. J. Med. Chem. 2004, 47, 627-643.
10. Plummer, C. W.; Finke, P. E.; Mills, S. G.; Wang, J.; Tong, X.; et al. Synthesis and activity of 4,5-diarylimidazoles as human CB1 receptor inverse agonists. Bioorg. Med. Chem. Lett. 2005, 15, 1441-1446.
11. Muccioli, G. G.; Wouters, J.; Charlier, C.; Scriba, G. K.; Pizza, T.; et al. Synthesis and activity of 1,3,5-triphenylimidazolidine-2,4-diones and 1,3,5-triphenyl-2-thioxoimidazolidin-4-ones: characterization of new CB1 cannabinoid receptor inverse agonists/antagonists. J. Med. Chem. 2006, 49, 872-882.
12. Meurer, L. C.; Finke, P. E.; Mills, S. G.; Walsh, T. F.; Toupence, R. B.; et al. Synthesis and SAR of 5,6-diarylpyridines as human CB1 inverse agonists. Bioorg. Med. Chem. Lett. 2005, 15, 645-651.
13. Pan, X.; Ikeda, S. R.; Lewis, D. L. SR 141716A acts as an inverse agonist to increase neuronal voltage-dependent Ca2+ currents by reversal of tonic CB1 cannabinoid receptor activity. Mol. Pharmacol. 1998, 54, 1064-1072.
14. Meschler, J. P.; Kraichely, D. M.; Wilken, G. H.; Howlett, A. C. Inverse agonist properties of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCI (SR141716A) and 1-(2-chlorophenyl)-4-cyano-5-(4-methoxyphenyl)-1H-pyrazole-3-carboxylic acid phenylamide (CP-272871) for the CB(1) cannabinoid receptor. Biochem. Pharmacol. 2000, 60, 1315-1323.
15. Schlicker, E.; Kathmann, M. Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol. Sci. 2001, 22, 55-572.
16. Pertwee, R. G. Inverse agonism and neutral antagonism at cannabinoid CB1 receptors. Life Sci. 2005, 76, 1307-1324.
17. Bouaboula, M.; Perrachon, S.; Milligan, L.; Canat, X.; Rinaldi-Carmona, M.; et al. A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor 1. Evidence for a new model of receptor/ligand interactions. J. Biol. Chem. 1997, 272, 22330-22339.
18. Leff, P. The two-state model of receptor activation. Trends Pharmacol. Sci. 1995, 16, 89-97.
19. McAllister, S. D.; Rizvi, G.; Anavi-Goffer, S.; Hurst, D. P.; Barnett-Norris, J.; et al. An aromatic microdomain at the cannabinoid CB(1) receptor constitutes an agonist/inverse agonist binding region. J. Med. Chem. 2003, 46, 5139-5152.
20. Ballesteros, J. A.; Jensen, A. D.; Liapakis, G.; Rasmussen, S. G.; Shi, L.; et al. Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J. Biol. Chem. 2001, 276, 29171-29177.
21. Visiers, I.; Ebersole, B. J.; Dracheva, S.; Ballesteros, J.; Sealfon, S. C.; et al. Structural motifs as functional microdomains in G-protein-coupled receptors: Energetic considerations in the mechanism of activation of the serotonin 5-HT2a receptor by disruption of the ionic lock of the arginine cage. Int. J. Quantum Chem. 2002, 88, 65-75.
22. Fay, J. F.; Dunham, T. D.; Farrens, D. L. Cysteine residues in the human cannabinoid receptor: only C257 and C264 are required for a functional receptor, and steric bulk at C386 impairs antagonist SR141716A binding. Biochemistry 2005, 44, 8757-8769.
23. Shire, D.; Calandra, B.; Bouaboula, M.; Barth, F.; Rinaldi-Carmona, M.; et al. Cannabinoid receptor interactions with the antagonists SR 141716A and SR 144528. Life Sci. 1999, 65, 627-635.
24. Barnett-Norris, J.; Hurst, D. P.; Buehner, K.; Ballesteros, J. A.; Guarnieri, F.; et al. Agonist alkyl tail interaction with cannabinoid CB1 receptor V6.43/I6.46 groove induces a Helix 6 active conformation. Int. J. Quantum Chem. 2002, 88, 76-86.
25. Jensen, A. D.; Guarnieri, F.; Rasmussen, S. G.; Asmar, F.; Ballesteros, J. A.; et al. Agonist-induced conformational changes at the cytoplasmic side of transmembrane segment 6 in the beta 2 adrenergic receptor mapped by site-selective fluorescent labeling. J. Biol. Chem. 2001, 276, 9279-9290.
26. Ghanouni, P.; Steenhuis, J. J.; Farrens, D. L.; Kobilka, B. K. Agonist-induced conformational changes in the G-protein-coupling domain of the beta 2 adrenergic receptor. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 5997-6002.
27. McAllister, S. D.; Tao, Q.; Barnett-Norris, J.; Buehner, K.; Hurst, D. P.; et al. A critical role for a tyrosine residue in the cannabinoid receptors for ligand recognition. Biochem. Pharmacol. 2002, 63, 2121-2136.
28. Barth, F.; Casellas, P.; Congy, C.; Martinez, S.; Rinaldi, M.; et al. Substituted N-Piperidino-3-Pyrazolecarboxamide. Eur. Pat. Appl. 656354, A1, 1995.
29. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry Part B: Reactions and Synthesis; 3rd ed.: Plenum Press: New York and London, 1990; p 98.
30. Vedejs, E.; Peterson, M. J. Stereochemistry and Mechanism in the Wittig Reaction. Topics in Stereochemistry; John Wiley & Sons: New York, 1994; pp 1-157.
31. Broekhof, N. L. J. M.; Jonkers, F. L.; van der Gen, A. Enamine synthesis by the Horner-Wittig Reaction. Tetrahedron Lett. 1979, 20, 2433-2436.
32. Broekhof, N. L. J. M.; Elburg, P. v.; Gen, A. v. d. Recl.: J. R. Neth. Chem. Soc. 1984, 103, 312-316.
33. Barth, F.; Casellas, P.; Congy, C.; Martinez, S.; Rinaldi, M.; et al. Pyrazole derivatives as cannabinoid receptor agonists. CAPLUS; Sanofi: US 5624941 A 19970429 CAN 127:5085 AN 1997:311258, 1997.
34. Seltzman, H. H.; Carroll, F. I.; Burgess, J. P.; Wyrick, C. D.; Burch, D. F. Synthesis, spectral studies and tritiation of the cannabinoid antagonist SR141716A. J. Chem. Soc., Chem. Commun. 1995, 1549-1550.
35. Seltzman, H. H.; Carroll, F. I.; Burgess, J. P.; Wyrick, C. D.; Burch, D. F. Tritiation of SR141716 by metalation-iodination-reduction: tritium-proton NOE study. J. Labelled Compd. Radiopharm. 2002, 45, 59-70.
36. Lan, R.; Liu, Q.; Fan, P.; Lin, S.; Fernando, S. R.; et al. Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J. Med. Chem. 1999, 42, 769-776.
37. Perola, E.; Charifson, P. S. Conformational analysis of drug-like molecules bound to proteins: An extensive study of ligand reorganization upon binding. J. Med. Chem. 2004, 47, 2499-2510.
38. Strange, P. G. Mechanisms of inverse agonism at G-protein-coupled receptors. Trends Pharmacol. Sci. 2002, 23, 89-95.
39. Lin, S. W.; Sakmar, T. P. Specific tryptophan UV-absorbance changes are probes of the transition of rhodopsin to its active state. Biochemistry 1996, 35, 11149-11159.
40. Song, Z. H.; Slowey, C. A.; Hurst, D. P.; Reggio, P. H. The difference between the CB(1) and CB(2) cannabinoid receptors at position 5.46 is crucial for the selectivity of WIN55212-2 for CB(2). Mol. Pharmacol. 1999, 56, 834-840.
41. Song, Z. H.; Bonner, T. I. A lysine residue of the cannabinoid receptor is critical for receptor recognition by several agonists but not WIN55212-2. Mol. Pharmacol. 1996, 49, 891-896.
42. Ballesteros, J. A.; Weinstein, H. Integrated Methods for the Construction of Three-Dimensional Models and Computational Probing of Structure Function Relations in G Protein-Coupled Receptors. Methods in Neuroscience; Academic Press: San Diego, CA, 1995; pp 366-428; Chapter 319.
43. Palczewski, K.; Kumasaka, T.; Hori, T.; Behnke, C. A.; Motoshima, H.; et al. Crystal structure of rhodopsin: A G protein-coupled receptor. Science 2000, 289, 739-745.
44. Gerard, C. M.; Mollereau, C.; Vassart, G.; Parmentier, M. Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem. J. 1991, 279, 129-134.
45. Bramblett, R. D.; Panu, A. M.; Ballesteros, J. A.; Reggio, P. H. Construction of a 3D model of the cannabinoid CB1 receptor: Determination of helix ends and helix orientation. Life Sci. 1995, 56, 1971-1982.
46. Javitch, J. A.; Fu, D.; Liapakis, G.; Chen, J. Constitutive activation of the beta2 adrenergic receptor alters the orientation of its sixth membrane-spanning segment. J. Biol. Chem. 1997, 272, 18546-18549.
47. Ward, S. D.; Hamdan, F. F.; Bloodworth, L. M.; Siddiqui, N. A.; Li, J. H.; et al. Use of an in situ disulfide cross-linking strategy to study the dynamic properties of the cytoplasmic end of transmembrane domain VI of the M(3) muscarinic acetylcholine receptor. Biochemistry 2006, 45, 676-685.
48. Farrens, D. L.; Altenbach, C.; Yang, K.; Hubbell, W. L.; Khorana, H. G. Requirement of rigid-body motion of transmembrane helicies for light-activation of rhodopsin. Science 1996, 274, 768-770.
49. Burley, S. K.; Petsko, G. A. Aromatic-aromatic interaction: a mechanism of protein structure stabilization. Science 1985, 229, 23-28.
50. Hunter, C. A.; Singh, J.; Thornton, J. M. Pi-pi interactions: the geometry and energetics of phenylalanine-phenylalanine interactions in proteins. J. Mol. Biol. 1991, 218, 837-846.
51. Tao, Q.; McAllister, S. D.; Andreassi, J.; Nowell, K. W.; Cabrai, G. A.; et al. Role of a conserved lysine residue in the peripheral cannabinoid receptor (CB2): evidence for subtype specificity. Mol. Pharmacol. 1999, 55, 605-613.
52. Tao, Q.; Abood, M. E. Mutation of a highly conserved aspartate residue in the second transmembrane domain of the cannabinoid receptors, CB1 and CB2, disrupts G-protein coupling. J. Pharmacol. Exp. Ther. 1998. 285, 651-658.
53. Cheng, Y.; Prusoff, W. H. Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50% inhibition (1C50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
54. Vasquez, C.; Lewis, D. L. The CB1 cannabinoid receptor can sequester G-proteins, making them unavailable to couple to other receptors. J. Neurosci. 1999, 19, 9271-9280.