Phenyl-tetrazolyl acetophenones: Discovery of positive allosteric potentiatiors for the metabotropic glutamate 2 receptor

Journal of Medicinal Chemistry

Volumn 47, Issue 18, 2004, Pages 4595-4599

  Pinkerton, Anthony B ^a   Vernier, Jean Michel ^a   Schaffhauser, Hervé ^a   Rowe, Blake A ^a   Campbell, Una C ^a   Rodriguez, Dana E ^a   Lorrain, Daniel S ^a   Baccei, Christopher S ^a   Daggett, Lorrie P ^a   Bristow, Linda J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 HYDROXY 3 PROPYL 4 [4 [4 (2H TETRAZOL 5 YL)PHENOXY]BUTOXY]PHENYL]ETHANONE; KETAMINE; METABOTROPIC RECEPTOR 2; METABOTROPIC RECEPTOR 3; METABOTROPIC RECEPTOR AGONIST; NORADRENALIN; PHENYLTETRAZOLYLACETOPHENONE DERIVATIVE; UNCLASSIFIED DRUG;

ALLOSTERISM; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; HYPERACTIVITY; NEUROPHARMACOLOGY; NEUROTRANSMITTER RELEASE; NONHUMAN; RAT; SCHIZOPHRENIA; STRUCTURE ACTIVITY RELATION;

ACETOPHENONES; ALLOSTERIC REGULATION; ANIMALS; BEHAVIOR; BRAIN; DOSE-RESPONSE RELATIONSHIP, DRUG; GLUTAMIC ACID; HYPERKINESIS; NOREPINEPHRINE; RATS; RECEPTORS, METABOTROPIC GLUTAMATE; SCHIZOPHRENIA; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 4143153832     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm040088h     Document Type: Article

References (23)

1. (a) Pin, J. P.; Acher, F. The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Current Drug Targets: CNS and Neurological Disorders 2002, 1, 297-317.
2. (b) Conn, P. J.; Pin, J. P. Pharmacology and functions of metabotropic glutamate receptors. Annual Rev. Pharmacol. Toxicol. 1997, 37, 205-237.
3. (c) Schoepp, D. D.; Jane, D. E.; Monn, J. A. Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology 1999, 38, 1431-1476.
4. Lam, A. G.; Soriano, M. A.; Monn, J. A.; Schoepp, D. D.; Lodge, D.; McCulloch, J. Effects of the selective metabotropic glutamate receptor agonist LY354740 in a rat model of permanent ischaemia. Neurosci. Lett. 1998, 254, 121-123.
5. Kingston, A. E.; O'Neill, M. J.; Lam, A.; Bales, K. R.; Monn, J. A.; Schoepp, D. D. Neuroprotection by metabotropic glutamate receptor agonists: LY354740, LY379268 and LY389795 Eur. J. Pharmacol. 1999, 377, 155-165.
6. Helton, D. R.; Tizzano, J. P.; Monn, J. A.; Schoepp, D. D.; Kallman, M. J. Anxiolytic and side effect profile of LY354740: a potent, highly selective, orally active agonist for group II metabotropic glutamate recptors. J. Pharmacol. Exp. Ther. 1998, 284, 651-660.
7. Chavez-Noriega, L. E.; Schaffhauser, H.; Campbell, U. C. Metabotropic glutamate receptors: potential drug target for the treatment of schizophrenia. Current Drug Targets: CNS and Neurological Disorders 2002, 1, 261-281.
8. Monn, J. A.; Valli, M. J.; Massey, S. M.; Wright, R. A.; Salhoff, C. R.; Johnson, B. G.; Howe, T.; Alt, C. A.; Rhodes, G. A.; Robey, R. L.; Griffey, K. R.; Tizzano, J. P.; Kallman, M. J.; Helton, D. R.; Schoepp, D. D. Design, synthesis, and pharmacological characterization of (+)-2-aminobicyclo[3.1.0]- hexane-2,6-dicarboxylic acid (LY354740): a potent, selective, and orally active group 2 metabotropic glutamate agonist possessing anticonvulsant and anxiolytic properties. J. Med. Chem. 1997, 40, 528-537.
9. Monn, J. A.; Valli, M. J.; Massey, S. M.; Hansen, M. M.; Kress, T. J.; Wepsiec, J. P.; Harkness, A. R.; Grutsch, J. L., Jr.; Wright, R. A.; Johnson, B. G.; Andis, S. L.; Kingston, A.; Tomlinson, R.; Lewis, R.; Griffey, K. R.; Tizzano, J. P.; Schoepp, D. D. Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2- aminobicyclo[3.1.0]-hexane-2,6-dicarboxylic acid (LY354740): identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors. J. Med. Chem. 1999, 42, 1027-1040.
10. Nakazato, A.; Kumagai, T.; Sakagami, K.; Yoshikawa, R.; Suzuki, Y.; Chaki, S.; Ito, H.; Taguchi, T.; Nakanishi, S.; Okuyama, S. Synthesis, SARs and pharmacological characterization of 2-amino-3 or 6-fluorobicyclo[3.1.0] hexane-2,6-dicarboxylic acid derivatives as potent, selective, and orally active group II metabotropic glutamate receptor agonists. J. Med. Chem. 2000, 43, 4893-4909.
11. Levine, L.; Gaydos, B.; Sheehan, D.; Goddarg, A. W.; Feighner, J.; Potter, W. Z.; Schoepp, D. D. The mGlu2/3 receptor agonist, LY354740, reduces panic anxiety induced by a CO2 challenge in patients diagnosed with panic disorder. Neuropharmacology 2002, 43, 294.
12. (a) Grillon, C.; Cordova, J.; Levine, L. R.; Morgan, C. A., III Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans. Psychopharmacology 2003, 168, 446-454.
13. (b) Schoepp, D. D.; Wright, R. A.; Levine, L. R.; Gaydos, B.; Potter, W. Z. LY354740, an mGlu2/3 receptor agonist as a novel approach to treat anxiety/stress. Stress 2003, 6, 189-197.
14. Knoflach, F.; Mutel, V.; Jolidon, S.; Kew, J. N. C.; Malherbe, P.; Viera, E.; Wichmann, J.; Kemp, J. A. Positive allosteric modulators of metabotropic glutamate 1 receptor: characterization, mechanism of action, and binding site. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 13402-13407.
15. Johnson, M. P.; Baez, M.; Jagdmann, G. E., Jr.; Britton, T. C.; Large, T. H.; Callagaro, D. O.; Tizzano, J. P.; Monn, J. A.; Schoepp, D. D. Discovery of allosteric potntiators for the metabotropic glutamate 2 receptor: synthesis and subtype selectivity of N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2- trifluoroethylsulfonyl)pyrid-3-ylmethylamine J. Med. Chem. 2003, 46, 3189-3192.
16. Schaffhauser, H.; Rowe, B. A.; Morales; Chavez-Noriega, L. E.; Yin, R.; Jachec, C.; Rao, S. P.; Bain, G.; Pinkerton, A. B.; Vernier, J.-M.; Bristow, L. J.; Varney, M. A.; Daggett L. P. Pharmacological characterization and identification of amino acids involved in the positive modulation of metabotropic glutamate receptor subtype 2. Mol. Pharmacol. 2003, 64, 798-810.
17. Varney, M. A.; Cosford, N. D.; Jachec, C.; Rao, S. P.; Sacaan, A.; Lin, F. F.; Bleicher, L.; Santori, E. M.; Flor, P. J.; Allgeier, H.; Gasparini, F.; Kuhn, R.; Hess, S. D.; Velicelebi, G.; Johnson, E. C. SIB-1757 and SIB-1893: selective, noncompetitive antagonists of metabotropic glutamate receptor type 5. J. Pharmacol. Exp. Ther. 1999, 290, 170-181.
18. Compound 3 was submitted to a panlabs screen and displayed no activity at <10 μM at the receptors mentioned. In addition, it showed no activity at dopamine, GABA, muscarinic, serotonin, histamine and adrenergic receptors.
19. Lorrain, D. S.; Schaffhauser, H.; Campbell, U. C.; Baccei, C. S.; Correa, L. D.; Rowe, B.; Rodriguez, D. E.; Anderson, J. J.; Varney, M. A.; Pinkerton, A. B.; Vernier, J.-M.; Bristow, L. J. Group II mGlu receptor activation suppresses norepinephrine release in the ventral hippocampus and locomotor responses to acute ketamine challenge. Neuropsychopharmacology 2003, 28, 1622-1632.
20. Moghaddam, B.; Adams, B. W. Reversal of phencyclidine effect by a group II metabotropic glutamate receptor agonists in rats. Science 1998, 281, 1349-1352.
21. Cartmell, J.; Monn, J. A.; Schoepp, D. D. The metabotropic glutamate 2/3 receptor agonists LY354740 and LY379268 selectively attenuate phencyclidine versus D-amphetamine motor behaviors in rats. J. Pharmacol. Exp. Ther. 1999, 291, 161-170.
22. Lorrain, D. S.; Baccei, C. S.; Bristow, L. J.; Anderson, J. J.; Varney, M. A. Effects of ketamine and NMDA on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective mGluR agonist LY379268. Neuroscience 2003, 117, 697-706.
23. Ornstein, P. L.; Bleisch, T. J.; Arnold, M. B.; Kennedy, J. H.; Wright, R. A.; Johnson, B. G.; Tizzano, J. P.; Helton, D. R.; Kallman, M. J.; Schoepp, D. D. 2-Substituted (2SR)-2-amino-2-((1SR,2SR)-2-carboxycydoprop-1-yl)glycines as potent and selective antagonists of group II metabotropic glutamate receptors. 2. Effects of aromatic substitution, pharmacological characterization and bioavailability. J. Med. Chem. 1998, 41, 358-378.