The importance of hydrogen bonding and aromatic stacking to the affinity and efficacy of cannabinoid receptor CB2 antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3, 3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528)

Journal of Medicinal Chemistry

Volumn 56, Issue 17, 2013, Pages 6593-6612

  Kotsikorou, Evangelia ^a   Navas III, Frank ^b   Roche, Michael J ^b   Gilliam, Anne F ^b   Thomas, Brian F ^b   Seltzman, Herbert H ^b   Kumar, Pritesh ^c   Song, Zhao Hui ^c   Hurst, Dow P ^d   Lynch, Diane L ^d   Reggio, Patricia H ^d  

^a UNIVERSITY OF TEXAS PAN AMERICAN   (United States)

^b RTI INTERNATIONAL   (United States)

^c University of Louisville School of Medicine   (United States)

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

Author keywords

[No Author keywords available]

Indexed keywords

5 (4 CHLORO 3 METHYL PHENYL) 1 (4 METHYL BENZYL) 1H PYRROLE 3 CARBOXYLIC ACID (1,3,3 TRIMETHYL BICYCLO[2.2.1]HEPT 2 YL) AMIDE; 5 (4 CHLORO 3 METHYLPHENYL) 1 (4 METHYL BENZYL) 3 [ 2 ENDO (1,3,3 TRIMETHYL BICYCLO[2.2.1]HEPT 2 YL) VINYL] 1H PYRAZOLE; 5 (4 CHLORO 3 METHYLPHENYL) 1 (4 METHYLBENZYL) N (1,3,3 TRIMETHYLBICYCLO[2.2.1]HEPTAN 2 YL) 3 PYRAZOLECARBOXAMIDE; 5 (4 CHLORO 3 METHYLPHENYL) 1 [(4 METHYLPHENYL)METHYL] 3 [ 2 [ 1,3,3 TRIMETHYL BICYCLO[2.2.1]HEPTAN 2 YL] ETHENYL] 1H PYRROLE; 5 (4 CHLORO 3 METHYLPHENYL) 1 [(4 METHYLPHENYL)METHYL] N [ 1,7,7 TRIMETHYLBICYCLO[2.2.1]HEPTAN 2 YL] 1H PYRAZOLE 3 CARBOXAMIDE; 5 (4 CHLORO 3 METHYLPHENYL) 1 PHENYL N [ 1,3,3 TRIMETHYL BICYCLO[2.2.1]HEPTAN 2 YL] 1H PYRAZOLE 3 CARBOXAMIDE; AMIDE; AMINO ACID; AROMATIC COMPOUND; CANNABINOID RECEPTOR ANTAGONIST; FUNCTIONAL GROUP; LIGAND; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CHEMICAL MODIFICATION; CONTROLLED STUDY; DRUG BINDING; DRUG EFFICACY; DRUG INHIBITION; DRUG SYNTHESIS; HYDROGEN BOND; MOLECULAR DYNAMICS; STATIC ELECTRICITY;

BORNANES; HYDROGEN BONDING; MODELS, MOLECULAR; PYRAZOLES; RADIOLIGAND ASSAY; RECEPTOR, CANNABINOID, CB2;

EID: 84884238459     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400070u     Document Type: Article

References (60)

1. Galiegue, S.; Mary, S.; Marchand, J.; Dussossoy, D.; Carriere, D.; Carayon, P.; Bouaboula, M.; Shire, D.; Le Fur, G.; Casellas, P. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations Eur. J. Biochem. 1995, 232, 54-61
2. 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
3. Benito, C.; Nunez, E.; Tolon, R. M.; Carrier, E. J.; Rabano, A.; Hillard, C. J.; Romero, J. Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains J. Neurosci. 2003, 23, 11136-11141
4. Van Sickle, M. D.; Duncan, M.; Kingsley, P. J.; Mouihate, A.; Urbani, P.; Mackie, K.; Stella, N.; Makriyannis, A.; Piomelli, D.; Davison, J. S.; Marnett, L. J.; Di Marzo, V.; Pittman, Q. J.; Patel, K. D.; Sharkey, K. A. Identification and functional characterization of brainstem cannabinoid CB2 receptors Science 2005, 310, 329-332
5. Buckley, N. E.; McCoy, K. L.; Mezey, E.; Bonner, T.; Zimmer, A.; Felder, C. C.; Glass, M. Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB(2) receptor Eur. J. Pharmacol. 2000, 396, 141-149
6. Massi, P.; Fuzio, D.; Vigano, D.; Sacerdote, P.; Parolaro, D. Relative involvement of cannabinoid CB(1) and CB(2) receptors in the delta(9)- tetrahydrocannabinol-induced inhibition of natural killer activity Eur. J. Pharmacol. 2000, 387, 343-347
7. Jorda, M. A.; Verbakel, S. E.; Valk, P. J.; Vankan-Berkhoudt, Y. V.; Maccarrone, M.; Finazzi-Agro, A.; Lowenberg, B.; Delwel, R. Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol Blood 2002, 99, 2786-2793
8. Kishimoto, S.; Gokoh, M.; Oka, S.; Muramatsu, M.; Kajiwara, T.; Waku, K.; Sugiura, T. 2-Arachidonoylglycerol induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes through the cannabinoid CB2 receptor-dependent mechanism J. Biol. Chem. 2003, 278, 24469-24475
9. Franklin, A.; Stella, N. Arachidonylcyclopropylamide increases microglial cell migration through cannabinoid CB2 and abnormal-cannabidiol-sensitive receptors Eur. J. Pharmacol. 2003, 474, 195-198
10. Kishimoto, S.; Kobayashi, Y.; Oka, S.; Gokoh, M.; Waku, K.; Sugiura, T. 2-Arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces accelerated production of chemokines in HL-60 cells J. Biochem. (Tokyo) 2004, 135, 517-524
11. McCoy, K. L.; Matveyeva, M.; Carlisle, S. J.; Cabral, G. A. Cannabinoid inhibition of the processing of intact lysozyme by macrophages: evidence for CB2 receptor participation J. Pharmacol. Exp. Ther. 1999, 289, 1620-1625
12. Idris, A. I.; van 't Hof, R. J.; Greig, I. R.; Ridge, S. A.; Baker, D.; Ross, R. A.; Ralston, S. H. Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors Nature Med. 2005, 11, 774-779
13. Rinaldi-Carmona, M.; Barth, F.; Millan, J.; Derocq, J. M.; Casellas, P.; Congy, C.; Oustric, D.; Sarran, M.; Bouaboula, M.; Calandra, B.; Portier, M.; Shire, D.; Breliere, J. C.; Le Fur, G. L. SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor J. Pharmacol. Exp. Ther. 1998, 284, 644-650
14. Bouaboula, M.; Desnoyer, N.; Carayon, P.; Combes, T.; Casellas, P. Gi protein modulation induced by a selective inverse agonist for the peripheral cannabinoid receptor CB2: implication for intracellular signalization cross-regulation Mol. Pharmacol. 1999, 55, 473-480
15. Iwamura, H.; Suzuki, H.; Ueda, Y.; Kaya, T.; Inaba, T. In vitro and in vivo pharmacological characterization of JTE-907, a novel selective ligand for cannabinoid CB2 receptor J. Pharmacol. Exp. Ther. 2001, 296, 420-425
16. Ross, R. A.; Brockie, H. C.; Stevenson, L. A.; Murphy, V. L.; Templeton, F.; Makriyannis, A.; Pertwee, R. G. Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656, and AM630 Br. J. Pharmacol. 1999, 126, 665-672
17. Lavey, B. J.; Kozlowski, J. A.; Hipkin, R. W.; Gonsiorek, W.; Lundell, D. J.; Piwinski, J. J.; Narula, S.; Lunn, C. A. Triaryl bis-sulfones as a new class of cannabinoid CB2 receptor inhibitors: identification of a lead and initial SAR studies Bioorg. Med. Chem. Lett. 2005, 15, 783-786
18. Shankar, B. B.; Lavey, B. J.; Zhou, G.; Spitler, J. A.; Tong, L.; Rizvi, R.; Yang, D. Y.; Wolin, R.; Kozlowski, J. A.; Shih, N. Y.; Wu, J.; Hipkin, R. W.; Gonsiorek, W.; Lunn, C. A. Triaryl bis-sulfones as cannabinoid-2 receptor ligands: SAR studies Bioorg. Med. Chem. Lett. 2005, 15, 4417-4420
19. Pasquini, S.; Ligresti, A.; Mugnaini, C.; Semeraro, T.; Cicione, L.; De Rosa, M.; Guida, F.; Luongo, L.; De Chiaro, M.; Cascio, M. G.; Bolognini, D.; Marini, P.; Pertwee, R.; Maione, S.; Di Marzo, V.; Corelli, F. Investigations on the 4-quinolone-3-carboxylic acid motif. 3. Synthesis, structure-affinity relationships, and pharmacological characterization of 6-substituted 4-quinolone-3-carboxamides as highly selective cannabinoid-2 receptor ligands J. Med. Chem. 2010, 53, 5915-5928
20. Lunn, C. A. Updating the chemistry and biology of cannabinoid CB2 receptor-specific inverse agonists Curr. Top. Med. Chem. 2010, 10, 768-778
21. Hurst, D. P.; Grossfield, A.; Lynch, D. L.; Feller, S.; Romo, T. D.; Gawrisch, K.; Pitman, M. C.; Reggio, P. H. A lipid pathway for ligand binding is necessary for a cannabinoid G protein-coupled receptor J. Biol. Chem. 2010, 285, 17954-17964
22. 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
23. Hurst, D. P.; Lynch, D. L.; Barnett-Norris, J.; Hyatt, S. M.; Seltzman, H. H.; Zhong, M.; Song, Z. H.; Nie, J.; Lewis, D.; Reggio, P. H. N -(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 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
24. Tao, Q.; McAllister, S. D.; Andreassi, J.; Nowell, K. W.; Cabral, G. A.; Hurst, D. P.; Bachtel, K.; Ekman, M. C.; Reggio, P. H.; Abood, M. E. Role of a conserved lysine residue in the peripheral cannabinoid receptor (CB2): evidence for subtype specificity Mol. Pharmacol. 1999, 55, 605-613
25. Seltzman, H. H.; Foster, M. C.; Wyrick, C. D.; Burgess, J. P.; Carroll, F. I. Tritiation of the cannabinoid receptor antagonist SR144528 involving lithium aluminum tritide reduction: assessment of the kinetic isotope effect by 3H-NMR J. Labelled Compd. Radiopharm. 2005, 48, 589-596
26. Barth, F.; Casellas, P.; Millan, J.; Qustric, D.; Rinaldi, M.; Sarran, M. 3-Pyrazolecarboxamide Derivatives Having Cannabinoid Receptor Affinity. Patent WO9721682 1997.
27. Corey, E. J.; Tius, M. A. 1-Diphenylphosphono-1-methoxymethyllithium, a useful reagent for the synthesis of aldehydes from hindered ketones Tetrahedron Lett. 1980, 21, 3535-3538
28. Vedejs, E.; Peterson, M. J. Stereochemistry and Mechanism in the Wittig Reaction. In Topics in Stereochemistry; John Wiley & Sons: New York, 1994; Vol. 21, pp 1-157.
29. Hurst, D.; Lynch, D.; Barnett-Norris, J.; Hyatt, S.; Seltzman, H.; Zhong, M.; Song ZH, N., J; Lewis, D.; Reggio, P. N -(Piperidin-1-yl)-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 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
30. Di Santo, R.; Costi, R.; Massa, S.; Artico, M. 4-Substituted 2-Phenyl- and 2-Phenyl-3-aryl Pyrroles by Reaction of Tosyl Benzyl Isocyanide (TosBIC) with Michael Acceptors Synth. Commun. 1995, 25, 795-802
31. van Leusen, A. M.; Wildeman, J.; Oldenziel, O. H. Base-Induced Cycloaddition of Sulfonylmethyl Isocyanides to C,N Double Bonds. Synthesis of 1,5-Disubstituted and 1,4,5-Trisubstituted Imidazoles from Aldimines and Imidoyl Chlorides J. Org. Chem. 1977, 42, 1153-1159
32. Sisko, J.; Mellinger, M.; Sheldrake, P. W.; Baine, N. H. α-Tosylbenzyl Isocyanide Org. Synth. 2000, 77, 198-205
33. Tarzia, G.; Duranti, A.; Tontini, A.; Piersanti, G.; Mor, M.; Rivara, S.; Plazzi, P. V.; Park, C.; Kathuria, S.; Piomelli, D. Design, Synthesis, and Structure-Activity Relationships of Alkylcarbamic Acid Aryl Esters, a New Class of Fatty Acid Amide Hydrolase Inhibitors J. Med. Chem. 2003, 46, 2352-2360
34. Padwa, A.; Haffmanns, G.; Tomas, M. Generation of Azomethine Ylides via the Desilylation Reaction of Immonium Salts J. Org. Chem. 1984, 49, 3314-3322
35. Kocienski, P. J.; Cernigliaro, G.; Feldstein, G. A Synthesis of (±)-Methyl n -Tetradeca- trans -2,4,5-trienoate, an Allenic Ester Produced by the Male Dried Bean Beetle Acanthoscelides obtectus (Say) J. Org. Chem. 1977, 42, 353-355
36. Haiduch, J.; Nam, G.; Ju Kim, E.; Frohlich, R.; Hanoverb, J. A.; Kirka, K. L. A convenient synthesis of the C-1-phosphonate analogue of UDP-GlcNAc and its evaluation as an inhibitor of O-linked GlcNAc transferase (OGT) Carbohydr. Res. 2008, 343, 189-195
37. Chevrier, C.; Le Nouën, D.; Defoin, A.; Tarnus, C. Synthesis of Amino- l -lyxose Phosphonates as Fucosyl-Phosphate Mimics Eur. J. Org. Chem. 2006, 2384-2392
38. Reichwein, J. F.; Pagenkopf, B. L. A New Horner-Wadsworth-Emmons Type Coupling Reaction between Nonstabilized beta-Hydroxy Phosphonates and Aldehydes or Ketones J. Am. Chem. Soc. 2003, 125, 1821-1824
39. Carman, R. M.; Greenfield, K. L. Aust. J. Chem. 1984, 37, 1785-1790
40. Murray, W. V.; Wachter, M. P. A Simple Regioelective Synthesis of Ethyl 1,5-Diarylpyrazole-3-carboxylates J. Heterocycl. Chem. 1989, 26, 1389-1392
41. Seltzman, H. H.; Carroll, F. I.; Burgess, J. P.; Wyrick, C. D.; Burch, D. F. Tritiation of SR141716 by metallation-iodination-reduction: tritium-proton nOe study J. Labelled Comp. Radiopharm. 2002, 44, 1-12
42. Talley, J. J.; Penning, T. D.; Collins, P. W.; Rogier, J. D. J.; Malecha, J. W.; Miyashiro, J. M.; Bertenshaw, S. R.; Khanna, I. K.; Graneto, M. J.; Rogers, R. S.; Carter, J. S.; Docter, S. H.; Yu, S. S. Substituted Pyrazolyl Benzenesulfonamides for the Treatment of Inflammation. U.S. Patent 5,760,068, June 2, 1998.
43. Feng, W.; Song, Z. H. Effects of D3.49A, R3.50A, and A6.34E mutations on ligand binding and activation of the cannabinoid-2 (CB2) receptor Biochem. Pharmacol. 2003, 65, 1077-1085
44. Rhee, M. H.; Nevo, I.; Levy, R.; Vogel, Z. Role of the highly conserved Asp-Arg-Tyr motif in signal transduction of the CB2 cannabinoid receptor FEBS Lett. 2000, 466, 300-304
45. Rhee, M. H.; Nevo, I.; Bayewitch, M. L.; Zagoory, O.; Vogel, Z. Functional role of tryptophan residues in the fourth transmembrane domain of the CB(2) cannabinoid receptor J. Neurochem. 2000, 75, 2485-2491
46. Nebane, N. M.; Kellie, B.; Song, Z. H. The effects of charge-neutralizing mutation D6.30N on the functions of CB1 and CB2 cannabinoid receptors FEBS Lett. 2006, 580, 5392-5398
47. Feng, W.; Song, Z. H. Functional roles of the tyrosine within the NP(X)(n)Y motif and the cysteines in the C-terminal juxtamembrane region of the CB2 cannabinoid receptor FEBS Lett. 2001, 501, 166-170
48. Chin, C.; Lucas-Lenard, J.; Abadji, V.; Kendall, D. A. Ligand Binding and Modulation of Cyclic AMP Levels Depend on the Chemical Nature of Residue 192 of the Human Cannabinoid Receptor 1 J. Neurochem. 1998, 70, 366-373
49. Shire, D.; Calandra, B.; Bouaboula, M.; Barth, F.; Rinaldi-Carmona, M.; Casellas, P.; Ferrara, P. Cannabinoid receptor interactions with the antagonists SR 141716A and SR 144528 Life Sci. 1999, 65, 627-635
50. Zhang, Y.; Xie, Z.; Wang, L.; Schreiter, B.; Lazo, J. S.; Gertsch, J.; Xie, X. Q. Mutagenesis and computer modeling studies of a GPCR conserved residue W5.43(194) in ligand recognition and signal transduction for CB2 receptor Int. Immunopharmacol. 2011, 11, 1303-1310
51. Gouldson, P.; Calandra, B.; Legoux, P.; Kerneis, A.; Rinaldi-Carmona, M.; Barth, F.; Le Fur, G.; Ferrara, P.; Shire, D. Mutational analysis and molecular modelling of the antagonist SR 144528 binding site on the human cannabinoid CB(2) receptor Eur. J. Pharmacol. 2000, 401, 17-25
52. Ballesteros, J. A.; Deupi, X.; Olivella, M.; Haaksma, E. E.; Pardo, L. Serine and threonine residues bend alpha-helices in the chi(1) = g(-) conformation Biophys. J. 2000, 79, 2754-2760
53. Kapur, A.; Hurst, D. P.; Fleischer, D.; Whitnell, R.; Thakur, G. A.; Makriyannis, A.; Reggio, P. H.; Abood, M. E. Mutation Studies of Ser7.39 and Ser2.60 in the Human CB1 Cannabinoid Receptor: Evidence for a Serine-Induced Bend in CB1 Transmembrane Helix 7 Mol. Pharmacol. 2007, 71, 1512-1524
54. Paquette, L. A.; Doehner, R. F., Jr Synthesis of Optically Active Triazolinediones and Examination of their Utility for Inducing Asymmetry in Diels-Alder Cycloaddition Reactions J. Org. Chem. 1980, 45, 5105-5113
55. Palczewski, K.; Kumasaka, T.; Hori, T.; Behnke, C. A.; Motoshima, H.; Fox, B. A.; Le Trong, I.; Teller, D. C.; Okada, T.; Stenkamp, R. E.; Yamamoto, M.; Miyano, M. Crystal structure of rhodopsin: A G protein-coupled receptor Science 2000, 289, 739-745
56. Zhang, R.; Hurst, D. P.; Barnett-Norris, J.; Reggio, P. H.; Song, Z. H. Cysteine 2.59(89) in the second transmembrane domain of human CB2 receptor is accessible within the ligand binding crevice: evidence for possible CB2 deviation from a rhodopsin template Mol. Pharmacol. 2005, 68, 69-83
57. Nebane, N. M.; Hurst, D. P.; Carrasquer, C. A.; Qiao, Z.; Reggio, P. H.; Song, Z. H. Residues accessible in the binding-site crevice of transmembrane helix 6 of the CB2 cannabinoid receptor Biochemistry 2008, 47, 13811-13821
58. 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
59. Pei, Y.; Mercier, R. W.; Anday, J. K.; Thakur, G. A.; Zvonok, A. M.; Hurst, D.; Reggio, P. H.; Janero, D. R.; Makriyannis, A. Ligand-binding architecture of human CB2 cannabinoid receptor: evidence for receptor subtype-specific binding motif and modeling GPCR activation Chem. Biol. 2008, 15, 1207-1219
60. Humphrey, W.; Dalke, A.; Schulten, K. VMD: visual molecular dynamics J. Mol. Graph. 1996, 14, 33-38