Ethyl (3s,4aR,6S,8aR)-6-(4-ethoxycar-bonylimidazol-1-ylmethyl) decahydroiso-quinoline-3-carboxylic ester: A prodrug of a GluR5 kainate receptor antagonist active in two animal models of acute migraine

Journal of Medicinal Chemistry

Volumn 45, Issue 20, 2002, Pages 4383-4386

  Filla, Sandra A ^a   Winter, Mark A ^a   Johnson, Kirk W ^a   Bleakman, David ^a   Bell, Michael G ^a   Bleisch, Thomas J ^a   Castaño, Ana M ^b   Clemens Smith, Amy ^a   Del Prado, Miriam ^b   Dieckman, Donna K ^a   Dominguez, Esteban ^b   Escribano, Ana ^b   Ho, Ken H ^a,c   Hudziak, Kevin J ^a   Katofiasc, Mary A ^a   Martinez Perez, Jose A ^b   Mateo, Ana ^b   Mathes, Brian M ^a   Mattiuz, Edward L ^a   Ogden, Ann Marie L ^a   Phebus, Lee A ^a   Stack, Douglas R ^a   Stratford, Robert E ^a   Ornstein, Paul L ^a   more..

^a ELI LILLY AND COMPANY   (United States)

^b CSIC   (Spain)

^c NPS Pharmaceutical Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ETHYL 6 (4 ETHOXYCARBONYLIMIDAZOL 1 YLMETHYL)DECAHYDROISOQUINOLINE 3 CARBOXYLIC ESTER; GLUTAMATE RECEPTOR; ISOQUINOLINE DERIVATIVE; KAINIC ACID RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MIGRAINE; NONHUMAN; RAT; RECEPTOR AFFINITY;

ACUTE DISEASE; ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; CALCIUM; CARBOXYLIC ACIDS; CELL LINE; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ESTERS; EXCITATORY AMINO ACID ANTAGONISTS; HUMANS; ISOQUINOLINES; MIGRAINE DISORDERS; PRODRUGS; RADIOLIGAND ASSAY; RATS; RATS, WISTAR; RECEPTORS, KAINIC ACID;

EID: 0037179709     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm025548q     Document Type: Article

References (40)

1. Collingridge, G. J.; Lester, A. J. Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol. Rev. 1989, 40, 145-195.
2. (a) Bleakman, D.; Lodge, D. Neuropharmacology of AMPA and kainate receptors. Neuropharmacology 1998, 37, 1187-1204.
3. (b) Hollman, M.; Heinemann, S. Cloned glutamate receptors. Annu. Rev. Neurosci. 1994, 17, 31-108.
4. (c) Seeburg, P. H. The molecular biology of mammalian glutamate receptor channels. Trends Neurosci. 1993, 16, 359-365.
5. (a) Li, P.; Wilding, T. J.; Kim, S. J.; Calejesan, A. A.; Huettner, J. E.; Zhuo, M. Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature 1999, 397, 161-164.
6. (b) Procter, M. J.; Houghton, A. K.; Faber, E. S. L.; Chizh, B. A.; Ornstein, P. L.; Lodge, D.; Headley, P. M. Actions of kainate and AMPA selective glutamate receptor ligands on nociceptive processing in the spinal cord. Neuropharmacology 1998, 37, 1287-1297.
7. (c) Evans, R. H.; Long, S. K. Primary afferent depolarization in the rat spinal cord is mediated by pathways utilizing NMDA and non-NMDA receptors. Neurosci. Lett. 1989, 100, 231-236.
8. (d) Evans R. H.; Evans, S. J.; Pook, P. C.; Sunter, D. C. A comparison of excitatory amino acid antagonists acting at primary afferent C fibers and motoneurons of the isolated spinal cord of the rat. Br. J. Pharmacol. 1987, 91, 531-537.
9. Agrawal, S. G.; Evans, R. H. The primary afferent depolarizing action of kainate in the rat. Br. J. Phamacol. 1986, 87, 345-355.
10. (a) Huettner, J. E. Glutamate receptor channels in DRG neurons: activation by kainate and quisqualate and blockade of desensitization by concanavalin. Neuron 1990, 5, 255-266.
11. (b) Partin, K. M.; Patneau, D. K.; Winters, C. A.; Mayer, M. L.; Buonanno, A. Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A. Neuron 1993, 11, 1069-1082.
12. Bleisch, T. J.; Ornstein, P. L.; Allen, N. K.; Wright, R. A.; Lodge, D.; Schoepp, D. D. Structure-Activity Studies of Aryl-Spaced Decahydroisoquinoline-3-carboxylic Acid AMPA Receptor Antagonists. Bioorg. Med. Chem. Lett. 1997, 7, 1161-1166.
13. Simmons, R. M. A.; Li, D. L.; Hoo, K. H.; Deverill, M.; Ornstein, P. L.; Iyengar, S. Kainate GluR5 receptor subtype mediates the nociceptive response to formalin in the rat. Neuropharmacology 1998, 37, 25-36.
14. (a) Ornstein, P. L.; Arnold, M. B.; Augenstein, N. K.; Lodge, D.; Leander, J. D.; Schoepp, D. D. (3SR,4aRS,6RS,8aRS)-6-[2(1H-Tetrazol-5-yl)ethyl]decahydroisoquinoline-3 -carboxylic Acid: A Structurally Novel, Systemically Active, Competitive AMPA Receptor Antagonist. J. Med. Chem. 1993, 36, 2046-2048.
15. (b) Ornstein, P. L.; Arnold, M. B.; Allen, N. K.; Bleisch, T.; Borromeo, P. S.; Lugar, C. W.; Leander, J. D.; Lodge, D.; Schoepp, D. D. Structure-Activity Studies of 6-(Tetrazolylalkyl)-Substituted Decahydroisoquinoline-3-carboxylic Acid AMPA Receptor Antagonists. 1. Effects of Stereochemistry, Chain Length, and Chain Substitution. J. Med. Chem. 1996, 39, 2219-2231.
16. (c) Ornstein, P. L.; Arnold, M. B.; Allen, N. K.; Bleisch, T.; Borromeo, P. S.; Lugar, C. W.; Leander, J. D.; Lodge, D.; Schoepp, D. D. Structure-Activity Studies of 6-Substituted Decahydroisoquinoline-3-carboxylic Acid AMPA Receptor Antagonists. 2. Effects of Distal Acid Bioisosteric Substitution, Absolute Stereochemical Preferences, and in Vivo Activity. J. Med. Chem. 1996, 39, 2232-2244.
17. (a) Sang, C. N.; Hostetter, M. P.; Gracely, R. H.; Chappell, A. S.; Schoepp, D. D.; Lee, G.; Whitcup, S.; Caruso, R.; Max, M. B. AMPA/Kainate Antagonist LY293558 Reduces Capsaicin-Evoked Hyperalgesia but Not Pain in Normal Skin in Humans. Anesthesiology 1998, 89, 1060-1067.
18. (b) Gilron, I.; Max, M. B.; Lee, G.; Booher, S. L.; Sang, C. N.; Chappell, A. S.; Dionne, R. A. Effects of the 2-amino-3-hydroxy-5-methyl-isoxazole-proprionic acid/kainate antagonist LY293558 on spontaneous and evoked postoperative pain. Clin. Pharmacol. Ther. 2000, 68, 320-327.
19. Sahara, Y.; Noro, N.; Iida, Y.; Soma, K.; Nakamura, Y. Glutamate Receptor Subunits GluR5 and KA-2 Are Coexpressed in Rat Trigeminal Ganglion Neurons. J. Neurosci. 1997, 17, 6611-6620.
20. Alam, Z.; Coombes, N.; Waring, R. H.; Williams, A. C.; Steventon, G. B. Plasma levels of neuroexcitatory amino acids in patients with migraine or tension headache. J. Neurol. Sci. 1998, 156, 102-106.
21. Mitsikostas, D. D.; Sanchez del Rio, M.; Waeber, C.; Huang, Z.; Cutrer, F. M.; Moskowitz, M. A. Non-NMDA glutamate receptors modulate capsaicin induced c-fos expression within trigeminal nucleus caudalis. Br. J. Pharmacol. 1999, 127, 623-630.
22. Moskowitz, M. A.; MacFarlane, R. Neurovascular and molecular mechanisms in migraine headaches. Cereb. Brain Metab. Rev. 1993, 5, 159-177.
23. For reviews on the role of serotonin in migraine, see: (a) Johnson, K. W.; Phebus, L. A.; Cohen, M. L. Serotonin in migraine: Theories, animal models and emerging therapies. In Progress in Drug Research; Jucker, E., Ed.; Birkhäuser Verlag: Basel, Switzerland, 1998; Vol. 51, pp 219-244.
24. (b) Goadsby, P. J. Serotonin 5-HT1B/1D receptor agonists in migraine: comparative pharmacology and its therapeutic implications. CNS Drugs 1998, 10, 271-286.
25. (c) DeVries, P.; Villalon, C. M.; Saxena, P. R. Pharmacology of triptans. Emerging Drugs 1999, 4, 107-125.
26. Ornstein, P. L.; Augenstein, N. K.; Arnold, M. B. Stereoselective Synthesis of 6-Substituted Decahydroisoquinoline-3-carboxylates: Intermediates for the Preparation of Conformationally Constrained Acidic Amino Acids. J. Org. Chem. 1994, 59, 7862-7869.
27. Small, B.; Thomas, J.; Kemp, M.; Hoo, K.; Ballyk, B.; Deverill, M.; Ogden, A. M.; Rubio, A.; Pedregal, C.; Bleakman, D. LY339434, a GluR5 kainate receptor agonist. Neuropharmacology 1998, 37, 1261-1267.
28. Sheardown, M. J.; Nielsen, E. Ø.; Hansen, A. J.; Jacobsen, P.; Honoré, T. 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a neuroprotectant for cerebral ischemia. Science 1990, 247, 571-574.
29. For experimental methods, see Supporting Information.
30. B for these experiments was estimated by nonlinear regression analysis of data represented in Figure 2. This method allows simultaneous fitting of agonist curves using the methods described in the following references. (a) Bemis, K. Fitting nonlinear models in isolated tissue studies using PROCNLIN in SAS. American Statistical Association, Proceedings of the Biopharmaceutical Section 1985, 72-74.
31. (b) Lew, M. J.; Angus, J. A. Analysis of competitive agonist-antagonist interactions by nonlinear regression. Trends Pharmacol. Sci. 1985, 16, 328-337.
32. Bleakman, D.; Ogden, A.; Ornstein, P. L.; Hoo, K. Pharmacological characterization of a GluR6 kainate receptor in cultured hippocampal neurons. J. Pharmacol. 1999, 378, 331-337.
33. (b) Bleakman, D.; Schoepp, D. D.; Ballyk, B.; Bufton, H.; Sharpe, E. F.; Thomas, K.; Ornstein, P. L.; Kamboj, R. K. Pharmacological Discrimination of GluR5 and GluR6 Kainate Receptor Subtypes by (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]-decahydroisoquinoline-3 -carboxylic-acid. Mol. Pharmacol. 1996, 49, 581-585.
34. The in vitro binding affinity of diester 4 at all AMPA and KA receptors tested, including the GluR5 KA receptor, was greater than 40 μM.
35. (a) Buzzi, M. G.; Bonamini, M.; Moskowitz, M. A. Neurogenic model of migraine. Cephalalgia 1995, 15, 277-280.
36. (b) Moskowitz, M. A.; Cutrer, F. M.; Lee, W. S.; Waeber, C.; Limmroth, V.; Yu, X. Drug Discovery in Migraine Circa 1995. In Experimental Headache Models; Olesen, J., Moskowitz, M. A., Eds.; Lippincott-Raven Publishers: Philadelphia, PA, 1995; pp 63-73.
37. (a) Buzzi, M. G.; Moskowitz, M. A. The antimigraine drug sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura matter. Br. J. Pharmacol. 1990, 99, 202-206.
38. 1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs. NeuroReport 1997, 8, 2237-2240.
39. 1D Receptors. J. Med. Chem. 1995, 38, 1799-1810.
40. Mitsikostas, D. D.; Sanchez del Rio, M. Receptor systems mediating c-fos expression within trigeminal nucleus caudalis in animal models of migraine. Brain Res. Rev. 2001, 35, 20-35 and references therein.