Synthesis and simple 18F-labeling of 3-fluoro-5-(2-(2- (fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile as a high affinity radioligand for imaging monkey brain metabotropic glutamate subtype-5 receptors with positron emission tomography

Journal of Medicinal Chemistry

Volumn 50, Issue 14, 2007, Pages 3256-3266

  Siméon, Fabrice G ^a   Brown, Amira K ^a   Zoghbi, Sami S ^a   Patterson, Velvet M ^a   Innis, Robert B ^a   Pike, Victor W ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [2 [2 (BROMOMETHYL)THIAZOL 4 YL]ETHYNYL] 5 FLUOROBENZONITRILE; 3 FLUORO 5 [2 [2 (FLUOROMETHYL)THIAZOL 4 YL]ETHYNYL]BENZONITRILE; BENZONITRILE; FLUORINE 18; INOSITOL PHOSPHATE; METABOTROPIC RECEPTOR 5; METHYL GROUP; RADIOLIGAND; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG; 3 FLUORO 5 (2 (2 (FLUOROMETHYL)THIAZOL 4 YL)ETHYNYL)BENZONITRILE; 3-FLUORO-5-(2-(2-(FLUOROMETHYL)THIAZOL-4-YL)ETHYNYL)BENZONITRILE; METABOTROPIC RECEPTOR; NITRILE; THIAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BRAIN; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG LABELING; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; DRUG UPTAKE; HUMAN; HUMAN TISSUE; IC 50; ISOTOPE LABELING; NEURORADIOLOGY; NONHUMAN; POSITRON; RHESUS MONKEY; ANIMAL; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MACACA; METABOLISM; POSITRON EMISSION TOMOGRAPHY; RADIOASSAY; RAT; SCINTISCANNING;

ANIMALS; BRAIN; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; HUMANS; MACACA MULATTA; NITRILES; POSITRON-EMISSION TOMOGRAPHY; RADIOLIGAND ASSAY; RATS; RECEPTORS, METABOTROPIC GLUTAMATE; THIAZOLES;

EID: 34447520294     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0701268     Document Type: Article

References (37)

1. Bräuner-Osborne, H.; Egebjerg, J.; Nielsen, E. O.; Madsen, U.; Krogsgaard-Larsen, P. Ligands for glutamate receptors: Design and therapeutic prospects. J. Med. Chem. 2000, 43, 2609-2645.
2. Conn, P. J.; Pin, J. P. Pharmacology and functions of metabotropic glutamate receptors. Ann. Rev. Pharmacol. Toxicol. 1997, 37, 205-237.
3. Pin, J.-P.; Acher, F. The metabotropic glutamate receptors: Structure, activation mechanism, and pharmacology. Curr. Drug Targets: CNS Neurol. Disord. 2002, 1, 297-317.
4. Gasparini, F.; Lingenhohl, K.; Stoehr, N.; Flor, P. J.; Heinrich, M.; Vranesic, I.; Biollaz, M.; Allgeier, H.; Heckendorn, R.; Urwyler, S.; Varney, M. A.; Johnson, E. C.; Hess, S. D.; Rao, S. P.; Sacaan, A. I.; Santori, E. M.; Velicelebi, G.; Kuhn, R. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 1999, 38, 1493-1503.
5. 3H]-methoxy-PEPy: Potent and selective radioligands for the metabotropic glutamate subtype 5 (mGlu5) receptor. Bioorg. Med. Chem. Lett. 2003, 13, 351-354.
6. Pietraszek, M.; Nagel, J.; Gravius, A.; Schäfer, D.; Danysz, W. The role of group I metabotropic glutamate receptors in schizophrenia. Amino Acids 2006, 32, 173-178.
7. Tsai, V. W. W; Scott, H. L.; Lewis, R. J.; Dodd, P. R. The role of group I metabotropic glutamate receptors in neuronal excitotoxicity in Alzheimer's disease. Neurotoxic. Res. 2005, 7, 125-141.
8. Brodkin, J.; Busse, C.; Sukoff, S. J.; Varney, M. A. Anxiolytic-like activity of the mGluR5 antagonist MPEP: A comparison with diazepam and buspirone. Pharmacol., Biochem. Behav. 2002, 73, 359-366.
9. Cosford, N. D. P.; Tehrani, L.; Roppe, J.; Schweiger, E.; Smith, N. D.; Anderson, J. J.; Bristow, L.; Brodkin, J.; Jiang, X. H.; McDonald, I.; Rao, S.; Washburn, M.; Varney M. A. 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: A potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity J. Med. Chem. 2003, 46, 204-206.
10. (a) Walker, K.; Reeve, A.; Bowes, M.; Winter, J.; Wotherspoon, G.; Davis, A.; Schmid, P.; Gasparini, F.; Kuhn, R.; Urban, L. mGlu5 receptors and nociceptive function II. mGlu5 receptors functionally expressed on peripheral sensory neurones mediate inflammatory hyperalgesia. Neuropharmacology 2001, 40, 10-19.
11. (b) Walker, K.; Bowes, M.; Panesar, M.; Davis, A.; Gentry, C.; Kesingland, A.; Gasparini, F.; Spooren, W.; Stoehr, N.; Pagano, A.; Flor, P. J.; Vranesic, I.; Lingenhoehl, K.; Johnson, E. C.; Varney, M.; Urban, L.; Kuhn, R. Metabotropic glutamate receptor subtype 5 (mGlu5) and nociceptive function I. Selective blockade of mGlu5 receptors in models of acute, persistent and chronic pain. Neuropharmacology 2001, 40, 1-9.
12. (a) Tessari, M.; Pilla, M.; Andreoli, M.; Hutcheson, D. M.; Heidbreder, C. A. Antagonism at metabotropic glutamate 5 receptors inhibits nicotine- and cocaine-taking behaviours and prevents nicotine-triggered relapse to nicotine-seeking. Eur. J. Pharmacol. 2004, 499, 121-133.
13. (b) Chiamulera, C.; Epping-Jordan, M. P.; Zocchi, A.; Marcon, C.; Cottiny, C.; Tacconi, S.; Corsi, M.; Orzi, F.; Conquet, F. Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice. Nat. Neurosci. 2001, 4, 873-874.
14. Kenny, P. J.; Markou, A. The ups and downs of addiction: Role of metabotropic glutamate receptors. Trends Pharmacol. Sci. 2004, 25, 265-272.
15. (a) Olive, F. M.; Mcgeehan, A. J.; Kinder, J. R.; McMahon, T.; Hodge, C. W.; Janak, P. H.; Messing, R. O. The mGluR5 antagonist 6-methyl-2- (phenylethynyl)pyridine decreases ethanol consumption via a protein kinase C-epsilon-dependent mechanism. Mol. Pharmacol. 2005, 67, 349-355.
16. (b) Backstrom, P.; Bachteler, D.; Koch, S.; Hyytiä, P.; Spanagel, R. mGluR5 antagonist MPEP reduces ethanol-seeking and relapse behavior. Neuropsychopharmacology 2004, 29, 921-928.
17. 11C-M-MPEP as a PET radioligand for the imaging of the metabotropic glutamate receptor 5 (mGLuR5). J. Labelled Compd. Radiopharm. 2001, 44 (Suppl. 1), S231-S232.
18. 11C]methoxy-PEPy - Synthesis and initial PET evaluation in rats and monkeys. Mol. Imaging Biol. 2003, 5, 168.
19. (a) Hamill, T. G.; Seiders, T. J.; Krause, S.; Ryan, C.; Sanabria, S.; Gibson, R. E.; Patel, S.; Cosford, N.; Roppe, J.; Yang, J.; King, C.; Hargreaves, R. J.; Burns, H. D. The synthesis and characterization of mGLuR5 receptor PET ligands. J. Labelled Compd. Radiopharm. 2003, 46 (Suppl 1), S184.
20. (b) Krause, S. M.; Hamill, T. G.; Seiders, T. J.; Ryan, C.; Sanabria, S.; Gibson, R. E.; Patel, S.; Cosford, N. D.; Roppe, J. R.; Hargreaves, R. J.; Burns, H. D. In vivo characterization of PET ligands for the mGluR5 receptor in rhesus monkey. Mol. Imaging Biol. 2003, 5, 166.
21. 11C-ABP688 as a probe for imaging the metabotropic glutamate receptor subtype 5. J. Nucl. Med. 2006, 47, 698-705.
22. 11C-ABP688. J. Nucl. Med. 2007, 48, 247-252.
23. Hamill, T. G.; Krause, S.; Ryan, C.; Bonnefous, C.; Govek, S.; Seiders, T. J.; Cosford, N. D. P.; Roppe, J.; Kamenecka, T.; Patel, S.; Gibson, R. E.; Sanabria, S.; Riffel, K.; Eng, W.; King C.; Yang, X.; Green, M. D.; O'Malley, S. S.; Hargreaves, R.; Burns, H. D. Synthesis, characterization, and first successful monkey imaging studies of metabotropic glutamate receptor subtype 5 (mGluR5) PET radiotracers. Synapse 2005, 56, 205-216.
24. Sonogashira, K.; Tohda, Y.; Hagihara, N. A convenient synthesis of acetylenes: Catalytic substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes, and bromopyridines. Tetrahedron Lett. 1975, 50, 4467-4470.
25. Dondoni, A.; Perrone, D. Total synthesis of (+)-galactostatin. An illustration of the utility of the thiazole-aldehyde synthesis. J. Org. Chem. 1995, 60, 4749-4754.
26. Nicolaou, K. C.; King, N. P.; Finlay, M. R. V.; He, Y.; Roschangar, F.; Vourloumis, D.; Vallberg, H.; Sarabia, F.; Ninkovic, S.; Hepworth, D. Total synthesis of epothilone E and related side-chain modified analogues via a Stille coupling based strategy. Bioorg. Med. Chem. 1999, 7, 665-697.
27. Pike, V. W. Positron-emitting radioligands for studies in vivo - Probes for human psychopharmacology. J. Psychopharmacol 1993, 7, 139-158.
28. 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.
29. Iso, Y.; Grajkowska, E.; Wroblewski, J. T.; Davis, J.; Goeders, N. E.; Johnson, K. M.; Sanker, S.; Roth, B. L.; Tueckmantel, W.; Kozikowski, A. P. Synthesis and structure-activity relationships of 3-[(2-methyl-1,3-thiazol-4-yl) ethynyl]pyridine analogues as potent, noncompetitive metabotropic glutamate receptor subtype 5 antagonists; search for cocaine medications. J. Med. Chem. 2006, 49, 1080-1100.
30. 18F]N-(2-fluoroethylation) of anilines. J. Labelled Compd. Radiopharm. 2004, 47, 217-232.
31. See http://www.uppsala.imanet.se/research-synthia.asp for a description of similar apparatus.
32. 3H]methoxyPEPy, an mGluR5 selective radioligand. Life Sci. 2003, 73, 371-379.
33. Scheibye, S.; Pedersen, B. S.; Lawesson, S.-O. Studies on organo-phosphorus compounds XXI. The dimer of p-methoxythionophosphine sulfide as a thiation reagent. A new route to thiocarboxamides. Bull. Soc. Chim. Belg. 1978, 87, 229-237.
34. a of receptor binding ligands. J. Labelled Compd. Radiopharm. 1997, 41, 136-138.
35. Lazarova, N.; Siméon, F. G.; Musachio, J. L.; Lu, S.; Pike, V. W. Integration of a microwave reactor with Synthia to provide a fully automated radiofluoridation module. J. Labelled Compd. Radiopharm. 2007, 50, 1-3.
36. Clark, J. D.; Baldwin, R. L.; Bayne, K. A.; Brown, M. J.; Gebhart, G. F.; Gonder, J. C.; Gwathmey, J. K.; Keeling, M. E.; Kohn, D. F.; Robb, J. W.; Smith, O. A.; Steggerda, J.-A. D.; Van de Berg, J. L. Guide for the Care and Use of Laboratory Animals; National Academy Press: Washington DC, 1996.
37. Carson, R. E.; Barker, W. C.; Liow, J.-S.; Johnson, C. A. Conference Record of the IEEE Nuclear Science Symposium and Medical Imaging Conference; Portland, Oregon, 2003.