The discovery of a selective, small molecule agonist for the mas-related gene X1 receptor

Journal of Medicinal Chemistry

Volumn 52, Issue 3, 2009, Pages 818-825

  Wroblowski, Berthold ^a   Wigglesworth, Mark J ^a   Szekeres, Philip G ^a   Smith, Graham D ^a   Rahman, Shahzad S ^a   Nicholson, Neville H ^a   Muir, Alison I ^a   Hall, Adrian ^a   Heer, Jag P ^a   Garland, Stephen L ^a   Coates, William J ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 [2 METHYL 3 (4 PHENYLBENZOYLAMIDO)BENZYL] 4 CHLORO 3 OXOPYRIDAZIN 5 YL]PIPERAZINE; DOCKING PROTEIN; LIGAND; MAS RELATED GENE X1 RECEPTOR; MEMBRANE RECEPTOR; PIPERAZINE DERIVATIVE; UNCLASSIFIED DRUG; BIPHENYL DERIVATIVE; CALCIUM; G PROTEIN COUPLED RECEPTOR; MAS RELATED GENE X1 RECEPTOR, HUMAN; MAS-RELATED GENE-X1 RECEPTOR, HUMAN; PYRIDAZINE DERIVATIVE;

ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG STRUCTURE; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; NOCICEPTION; PROTEIN ANALYSIS; RECEPTOR AFFINITY; SPINAL GANGLION; COMBINATORIAL CHEMISTRY; DRUG DESIGN; DRUG POTENTIATION; METABOLISM; PHYSIOLOGY; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

BIPHENYL COMPOUNDS; CALCIUM; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DESIGN; HUMANS; PIPERAZINES; PYRIDAZINES; RECEPTORS, G-PROTEIN-COUPLED; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 61449093904     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm800962k     Document Type: Article

References (37)

1. Butera, J. A. Current and Emerging Targets to Treat Neuropathic Pain. J. Med. Chem. 2007, 50, 2543-2546.
2. Kennedy, J. D. Neuropathic Pain: Molecular Complexity Underlies Continuing Unmet Medical Need. J. Med. Chem. 2007, 50, 2547-2556.
3. Childers, W. E.; Baudy, R. B. N-Methyl-D-Aspartate Antagonists and Neuropathic Pain: The Search for Relief. J. Med. Chem. 2007, 50, 2557-2562.
4. 2+ Channel α2-δ Ligands for the Treatment of Neuropathic Pain. J. Med. Chem. 2007, 50, 2569-2575.
5. Munro, G.; Dalby-Brown, W. Kv7 (KCNQ) Channel Modulators and Neuropathic Pain. J. Med. Chem. 2007, 50, 2576-2582.
6. Kyle, D. J.; Ilyin, V. I. Sodium Channel Blockers. J. Med. Chem. 2007, 50, 2583-2588.
7. Westaway, S. M. The Potential of Transient Receptor Potential Vanilloid Type 1 Channel Modulators for the Treatment of Pain.J. Med. Chem. 2007, 50, 2589-2596.
8. Schkeryantz, J. M.; Kingston, A. E.; Johnson, M. P. Prospects for Metabotropic Glutamate 1 Receptor Antagonists in the Treatment of Neuropathic Pain. J. Med. Chem. 2007, 50, 2563-2568.
9. Lai, J.; Luo, M-c.; Chen, Q.; Porreca, F. Pronociceptive actions of dynorphin via bradykinin receptors. Neurosci. Lett. 2008, 437, 175-179.
10. Coa, H.; Zhang, Y-Q. Spinal glial activation contributes to pathological pain states. Neurosci. Biobehav. Rev. 2008, 32, 972-983.
11. Burns, J. W.; Quartana, P. J.; Bruehl, S. Anger inhibition and pain: conceptualizations, evidence and new directions. J. Behav. Med. 2008, 31, 259-279.
12. Guindon, J.; Walczak, J-S.; Beaulieu, P. Recent Advances in the Pharmacological Management of Pain. Drugs 2007, 67, 2121-2133.
13. Newsome, S.; Frawley, B. K.; Argoff, C. E. Intrathecal analgesia for refractory cancer pain. Curr. Pain Headache Rep. 2008, 12, 249-256.
14. Dong, X.; Han, S.; Zylka, M. J.; Simon, M. I.; Anderson, D. J. A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 2001, 106, 619-632.
15. Lembo, P. M. C.; Grazzini, E; Groblewski, T.; O'Donnell, D.; Roy, M-O.; Zhang, J.; Hoffert, C.; Cao, J.; Schmidt, R.; Pelletier, M.; Labarre, M.; Gosselin, M.; Fortin, Y.; Banville, D.; Shen, S. H.; Strom, P.; Payza, K.l; Dray, A.; Walker, P.; Ahmad, S. Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs. Nat. Neurosci. 20025, 201-209.
16. Grazzini, E.; Puma, C.; Roy, M-O.; Yu, X. H.; O'Donnell, D.; Schmidt, R.; Dautrey, S.; Ducharme, J.; Perkins, M.; Panetta, R.; Laird, J. M. A.; Ahmad, S.; Lembo, P. M. C. Sensory neuron-specific receptor activation elicits central and peripheral nociceptive effects in rats. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 7175-7180.
17. Yang, S.; Liu, Y.; Lin, A. A.; Cavalli-Sforza, L. L.; Zhao, Z.; Su, B. Adaptive evolution of MRGX2, a human sensory neuron specific gene involved in nociception. Gene 2005, 352, 30-35.
18. Zylka, M. J.; Dong, X.; Southwell, A. L.; Anderson, D. J. Atypical expansion in mice of the sensory neuron-specific MrgG protein - coupled receptor family. Proc. Natl. Acad. Sci. U.S.A. 2003, 100,10043- 10048.
19. Burstein, E. S.; Ott, T. R.; Feddock, M.; Ma, J-N.; Fuhs, S.; Wong, S.; Schiffer, H. H.; Brann, M. R.; Nash, N. R. Characterization of the Mas-related gene family: structural and functional conservation of human and rhesus MrgX receptors. Br. J. Pharmacol. 2006, 147, 73-82.
20. Zhang, L.; Taylor, N.; Xie, Y.; Ford, R.; Johnson, J.; Paulsen, J. E.; Bates, B. Cloning and expression of MRG receptors in macaque, mouse and human. Mol. Brain Res. 2005, 133, 187-197.
21. Kunapuli, P.; Lee, S.; Zheng, W.; Alberts, M.; Kornienko, O.; Mull, R.; Kreamer, A.; Hwang, J. I.; Simon, M. I.; Strulovici, B. Identification of small molecule antagonists of the human mas-related gene - X1 receptor. Anal. Biochem. 2006, 351, 50-61.
22. Tomaszewski, M.; Discovery of pain targets-GPCR target class approach, XVIII International Symposium on Medicinal Chemistry, Copenhagen, Denmark, August, 2004.
23. Cai, Q.; Jiang, J.; Chen, T.; Hong, Y. Sensory neuron-specific receptor agonist BAM8-22 inhibits the development and expression of tolerance to morphine in rats. Behav. Brain Res. 2007, 178, 154-159.
24. Teitelbaum, H.; Catravas, G. N.; McFarland, W. L. Reversal of morphine tolerance after medial thalamic lesions in the rat. Science 1974, 185, 449-451.
25. Guo, R-x.; Cui, Y.; Mo, L-q.; Liu, W.; Feng, J-q. Changes of the spinal δ opioid receptors and NMDA receptors during the development of morphine tolerance. Jiepouxue Yanjiu 2007, 29, 88-92.
26. Mendez, I. A.; Trujillo, K. A. NMDA receptor antagonists inhibit opiate antinociceptive tolerance and locomotor sensitization in rats. Psychopharmacology (Berlin, Ger.) 2008, 196, 497-509.
27. Dalton, G. D.; Smith, F. L.; Smith, P. A.; Dewey, W. L. Alterations in brain protein kinase A activity and reversal of morphine tolerance by two fragments of native protein kinase A inhibitor peptide (PKI). Neuropharmacology 2005, 48, 648-657.
28. Parkitna, J. R.; Obara, I.; Wawrzczak-Bargiela, A.; Makuch, W.; Przewlocka, B.; Przewlocki, R. Effects of glycogen synthase kinase 3 and cyclin-dependent kinase 5 inhibitors on morphine-induced analgesia and tolerance in rats. J. Pharmacol. Exp. Ther. 2006, 319, 832-839.
29. Smith, F. L.; Javed, R.; Elzey, M. J.; Welch, S. P.; Selley, D.; Sim-Selley, L.; Dewey, W. L. Prolonged reversal of morphine tolerance with no reversal of dependence by protein kinase C inhibitors. Brain Res. 2002, 958, 28-35.
30. Adam, F.; Dufour, E.; Le Bars, D. The glycine site-specific NMDA antagonist (+)-HA966 enhances the effect of morphine and reverses morphine tolerance via a spinal mechanism. Neuropharmacology 2008, 54, 588-596.
31. Chen, T.; Hu, Z.; Quirion, R.; Hong, Y. Modulation of NMDA receptors by intrathecal administration of the sensory neuron-specific receptor agonist BAM8-22. Neuropharmacology 2008, 54, 796-803.
32. Olsson, R.; Knapp, A. E.; Eskildsen, J. Preparation of benzimidazole derivatives, especially N2-derivatized argininamides containing a substituted benzimidazole unit as modulators of MrgX receptors for the treatment of pain and methods of screening them. Patent WO2008052072, 2008.
33. 2+] using the fluorometric imaging plate reader (FLIPR). Methods Mol. Biol. 1999, 114, 125-133.
34. Sali, A.; Blundell, T. L. Comparative protein modeling by satisfaction of spatial restraints. J. Mol. Biol. 1993, 234, 779-815.
35. McMartin, C.; Bohacek, R. S. QXP: powerful, rapid computer algorithms for structure-based drug design. J. Comput.-Aided Mol. Des. 1997, 11, 333-344.
36. Rauhut, G.; Clark, T. Multicenter point charge model for high-quality molecular electrostatic potentials from AM1 calculations. J. Comput.Chem. 1993, 14, 503-509.
37. Schwartz, T. W.; Frimurer, T. M.; Holst, B.; Rosenkilde, M. M.; Elling, C. E. Molecular mechanism of 7TM receptor activation-a global toggle switch model. Annu. Rev. Pharmacol. Toxicol. 2006, 46,481-519.