Structure-activity relationships of fluorinated (E)-3-((6-Methylpyridin-2- yl)ethynyl)cyclohex-2-enone- O -methyloxime (ABP688) derivatives and the discovery of a high affinity analogue as a potential candidate for imaging metabotropic glutamate recepors subtype 5 (mGluR5) with Positron Emission Tomography (PET)

Journal of Medicinal Chemistry

Volumn 53, Issue 10, 2010, Pages 4009-4017

  Baumann, Cindy A ^a   Mu, Linjing ^a   Johannsen, Sinja ^a   Honer, Michael ^a   Schubiger, Pius A ^a   Ametamey, Simon M ^a  

^a ETH ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

2 (2 (3 (PYRIDIN 2 YLETHYNYL)CYCLOHEX 2 ENYLIDENEAMINOOXY)ETHOXY)ETHYL 4 METHYLBENZENESULFONATE; 3 ((6 METHYLPYRIDIN 2 YL)ETHYNYL)CYCLOHEX 2 ENONE O 2 (2 (TERT BUTYLDIMETHYLSILYLOXY)ETHOXY)ETHYLOXIME F 18; 3 (PYRIDIN 2 YLETHYNYL)CYCLOHEX 2 ENONE O 2 (2 (TERT BUTYLDIMETHYLSILYLOXY)ETHOXY)ETHYLOXIME F 18; 3 (PYRIDIN 2 YLETHYNYL)CYCLOHEX 2 ENONE O 2 (2 FLUOROETHOXY)ETHYLOXIME F 18; 3 (PYRIDIN 2 YLETHYNYL)CYCLOHEX 2 ENONEOXIME F 18; ABP 688; ALKYL GROUP; METABOTROPIC RECEPTOR 5; METHYL GROUP; PYRIDINE DERIVATIVE; RADIOPHARMACEUTICAL AGENT; UNCLASSIFIED DRUG;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; DRUG BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; MOLECULE; POSITRON EMISSION TOMOGRAPHY; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION;

ALKYNES; ANIMALS; BINDING, COMPETITIVE; BRAIN; FLUORINE RADIOISOTOPES; MALE; MODELS, MOLECULAR; OXIMES; POSITRON-EMISSION TOMOGRAPHY; PROTEIN BINDING; PYRIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, METABOTROPIC GLUTAMATE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77952723100     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm901850k     Document Type: Article

References (40)

1. Kew, J. N. C.; Kemp, J. A. Ionotropic and metabotropic glutamate receptor structure and pharmacology Psychopharmacology 2005, 179, 4-29. Erratum: Psychopharmacology 2005, 182 (2), 320 - 320
2. Conn, P. J.; Pin, J.-P. Pharmacology and functions of metabotropic glutamate receptors Annu. Rev. Pharmacol. 1997, 37 (1) 205-237
3. Ritzén, A.; Mathiesen, J. M.; Thomsen, C. Molecular pharmacology and therapeutic prospects of metabotropic glutamate receptor allosteric modulators Basic Clin. Pharmacol. 2005, 97 (4) 202-213
4. Bruno, V.; Ksiazek, I.; Battaglia, G.; Lukic, S.; Leonhardt, T.; Sauer, D.; Gasparini, F.; Kuhn, R.; Nicoletti, F.; Flor, P. J. Selective blockade of metabotropic glutamate receptor subtype 5 is neuroprotective Neuropharmacology 2000, 39 (12) 2223-2230 (Pubitemid 30642765)
5. Wang, Q.; Walsh, D. M.; Rowan, M. J.; Selkoe, D. J.; Anwyl, R. Block of long-term potentiation by naturally secreted and synthetic amyloid {beta}-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5 J. Neurosci. 2004, 24 (13) 3370-3378
6. Rouse, S. T.; Marino, M. J.; Bradley, S. R.; Awad, H.; Wittmann, M.; Conn, P. J. Distribution and roles of metabotropic glutamate receptors in the basal ganglia motor circuit: implications for treatment of Parkinsons disease and related disorders Pharmacol. Ther. 2000, 88 (3) 427-435
7. Ossowska, K.; Konieczny, J.; Wardas, J.; Pietraszek, M.; Kuter, K.; Wolfarth, S.; Pilc, A. An influence of ligands of metabotropic glutamate receptor subtypes on parkinsonian-like symptoms and the striatopallidal pathway in rats Amino Acids 2007, 32 (2) 179-188
8. Ohnuma, T.; Augood, S. J.; Arai, H.; McKenna, P. J.; Emson, P. C. Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia Mol. Brain Res. 1998, 56 (1-2) 207-217
9. Pietraszek, T.; Berghe, C. V. Defending against injection attacks through context-sensitive string evaluation Lect. Notes Comput. Sci. 2006, 3858, 124-145
10. Pilc, A.; Klodzinska, A.; Branski, P.; Nowak, G.; Palucha, A.; Szewczyk, B.; Tatarczynska, E.; Chojnacka-Wójcik, E.; Wieronska, J. M. Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats Neuropharmacology 2002, 43 (2) 181-187
11. Cosford, N. D. P.; Tehrani, L.; Roppe, J.; Schweiger, E.; Smith, N. D.; Anderson, 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 (2) 204-206 (Pubitemid 36078139)
12. Gasparini, F.; Lingenhöhl, 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.; Veliçelebi, G.; Kuhn, R. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist Neuropharmacology 1999, 38 (10) 1493-1503
13. Chiamulera, C.; Epping-Jordan, M. P.; Zocchi, A.; Marcon, C.; Cottiny, C.; Tacconi, S.; Corsi, M.; Orzi, F.; Conquet, F. O. Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice Nat. Neurosci. 2001, 4 (9) 873-874
14. Todd, P. K.; Mack, K. J.; Malter, J. S. The fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD-95 Proc. Natl. Acad. Sci. U.S.A. 2003, 100 (24) 14374-14378
15. Bordi, F.; Ugolini, A. Group I metabotropic glutamate receptors: implications for brain diseases Prog. Neurobiol. 1999, 59 (1) 55-79
16. Takahashi, K.; Tsuchida, K.; Tanabe, Y.; Masu, M.; Nakanishi, S. Role of the large extracellular domain of metabotropic glutamate receptors in agonist selectivity determination J. Biol. Chem. 1993, 268 (26) 19341-19345
17. Pin, J. P.; Acher, F. The metabotropic glutamate receptors: structure, activation mechanism and pharmacology Curr. Drug Targets: CNS Neurol. Disord. 2002, 1 (3) 297-317
18. Pagano, A.; Ruegg, D.; Litschig, S.; Stoehr, N.; Stierlin, C.; Heinrich, M.; Floersheim, P.; Prezeau, L.; Carroll, F.; Pin, J.-P.; Cambria, A.; Vranesic, I.; Flor, P. J.; Gasparini, F.; Kuhn, R. The non-competitive antagonists 2-methyl-6-(phenylethynyl)pyridine and 7-hydroxyiminocyclopropan[ b ]chromen-1a-carboxylic acid ethyl ester interact with overlapping binding pockets in the transmembrane region of group I metabotropic glutamate receptors J. Biol. Chem. 2000, 275 (43) 33750-33758
19. Alagille, D.; Baldwin, R. M.; Roth, B. L.; Wroblewski, J. T.; Grajkowska, E.; Tamagnan, G. D. Synthesis and receptor assay of aromatic-ethynyl-aromatic derivatives with potent mGluR5 antagonist activity Bioorg. Med. Chem. 2005, 13 (1) 197-209
20. Malherbe, P.; Kratochwil, N.; Mühlemann, A.; Zenner, M.-T.; Fischer, C.; Stahl, M.; Gerber, P. R.; Jaeschke, G.; Porter, R. H. P. Comparison of the binding pockets of two chemically unrelated allosteric antagonists of the mGlu5 receptor and identification of crucial residues involved in the inverse agonism of MPEP J. Neurochem. 2006, 98 (2) 601-615
21. Malherbe, P.; Kratochwil, N.; Zenner, M.-T.; Piussi, J.; Diener, C.; Kratzeisen, C.; Fischer, C.; Porter, R. H. P. Mutational analysis and molecular modeling of the binding pocket of the metabotropic glutamate 5 receptor negative modulator 2-methyl-6-(phenylethynyl)-pyridine Mol. Pharmacol. 2003, 64 (4) 823-832 (Pubitemid 37153050)
22. 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.; OMalley, 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 (4) 205-216
23. 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 J. Med. Chem. 2007, 50 (14) 3256-3266
24. 11C-ABP688 J. Nucl. Med. 2007, 48 (2) 247-252
25. 11C-ABP688 as a probe for imaging the metabotropic glutamate receptor subtype 5 J. Nucl. Med. 2006, 47 (4) 698-705
26. 18F]-FPECMO as a positron emission tomography radioligand for imaging the metabotropic glutamate receptor subtype 5 Nucl. Med. Biol. 2009, 36 (6) 613-622
27. Sonogashira, K.; Tohda, Y.; Hagihara, N. Convenient synthesis of acetylenes-catalytic substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes, and bromopyridines Tetrahedron Lett. 1975, 50) 4467-4470
28. Yeo, W.-S.; Min, D.-H.; Hsieh, R. W.; Greene, G. L.; Mrksich, M. Label-free detection of protein-protein interactions on biochips13 Angew. Chem., Int. Ed. 2005, 44 (34) 5480-5483
29. Cosford, N. D. P.; Mc Donald, I. A.; Bleicher, L. S.; Cube, R. V.; Schweiger, E. J.; Vernier, J.-M.; Hess, S. D.; Varney, M. A.; Mark, A.; Munoz, B. Preparation of Heterocyclic Compounds and Methods of Use Thereof. PCT Int. Appl. WO 0116121 (A1), 2001.
30. Wendt, J. A.; Deeter, S. D.; Bove, S. E.; Knauer, C. S.; Brooker, R. M.; Augelli-Szafran, C. E.; Schwarz, R. D.; Kinsora, J. J.; Kilgore, K. S. Synthesis and SAR of 2-aryl pyrido[2,3- d ]pyrimidines as potent mGlu5 receptor antagonists Bioorg. Med. Chem. Lett. 2007, 17 (19) 5396-5399
31. Bach, P.; Nilsson, K.; Wallberg, A.; Bauer, U.; Hammerland, L. G.; Peterson, A.; Svensson, T.; Österlund, K.; Karis, D.; Boije, M.; Wensbo, D. A new series of pyridinyl-alkynes as antagonists of the metabotropic glutamate receptor 5 (mGluR5) Bioorg. Med. Chem. Lett. 2006, 16 (18) 4792-4795
32. Bonnefous, C.; Vernier, J. M.; Hutchinson, J. H.; Chung, J.; Reyes-Manalo, G.; Kamenecka, T. Dipyridyl amides: potent metabotropic glutamate subtype 5 (mGlu5) receptor antagonists Bioorg. Med. Chem. Lett. 2005, 15 (4) 1197-1200 (Pubitemid 40458673)
33. Kulkarni, S. S.; Nightingale, B.; Dersch, C. M.; Rothman, R. B.; Newman, A. H. Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists Bioorg. Med. Chem. Lett. 2006, 16 (13) 3371-3375
34. Wilson, A. A.; Jin, L.; Garcia, A.; DaSilva, J. N.; Houle, S. An admonition when measuring the lipophilicity of radiotracers using counting techniques Appl. Radiat. Isot. 2001, 54 (2) 203-208
35. Dischino, D. D.; Welch, M. J.; Kilbourn, M. R.; Raichle, M. E. Relationship between lipophilicity and brain extraction of C-11-labeled radiopharmaceuticals J. Nucl. Med. 1983, 24 (11) 1030-1038
36. Limbird, L. E. Cell Surface Receptors: A Short Course on Theory and Methods, 3 rd ed.; Springer Science and Business Media: New York, 2005; p 219.
37. Chen, Y.; Nong, Y.; Goudet, C.; Hemstapat, K.; de Paulis, T.; Pin, J.-P.; Conn, P. J. Interaction of novel positive allosteric modulators of metabotropic glutamate receptor 5 with the negative allosteric antagonist site is required for potentiation of receptor responses Mol. Pharmacol. 2007, 71 (5) 1389-1398
38. Kinney, G. G.; OBrien, J. A.; Lemaire, W.; Burno, M.; Bickel, D. J.; Clements, M. K.; Chen, T.-B.; Wisnoski, D. D.; Lindsley, C. W.; Tiller, P. R.; Smith, S.; Jacobson, M. A.; Sur, C.; Duggan, M. E.; Pettibone, D. J.; Conn, P. J.; Williams, D. L., Jr. A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models J. Pharmacol. Exp. Ther. 2005, 313 (1) 199-206
39. Lindsley, C. W.; Wisnoski, D. D.; Leister, W. H.; OBrien, J. A.; Lemaire, W.; Williams, D. L.; Burno, M.; Sur, C.; Kinney, G. G.; Pettibone, D. J.; Tiller, P. R.; Smith, S.; Duggan, M. E.; Hartman, G. D.; Conn, P. J.; Huff, J. R. Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N -(1,3-diphenyl-1 H-pyrazol-5-yl)benzamides that potentiate receptor function in vivo J. Med. Chem. 2004, 47 (24) 5825-5828
40. Bradford, M. M. Rapid and sensitive method for quantitation of microgram quantities of protein utilizing principle of protein-dye binding Anal. Biochem. 1976, 72 (1-2) 248-254