Selective, Orally Active γ-Aminobutyric AcidA α5 Receptor Inverse Agonists as Cognition Enhancers

Journal of Medicinal Chemistry

Volumn 47, Issue 9, 2004, Pages 2176-2179

  Sternfeld, Francine ^a   Carling, Robert W ^a   Jelley, Richard A ^a   Ladduwahetty, Tamara ^a   Merchant, Kevin J ^a   Moore, Kevin W ^a   Reeve, Austin J ^a   Street, Leslie J ^a   O'Connor, Desmond ^a   Sohal, Bindi ^a   Atack, John R ^a   Cook, Susan ^a   Seabrook, Guy ^a   Wafford, Keith ^a   Tattersall, F David ^a   Collinson, Neil ^a   Dawson, Gerard R ^a   Castro, José L ^a   MacLeod, Angus M ^a  

^a NEUROSCIENCE RESEARCH CENTRE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID A ALPHA5 RECEPTOR INVERSE AGONIST; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; BENZODIAZEPINE; BENZODIAZEPINE RECEPTOR; FLUMAZENIL; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL CELL; ANXIETY DISORDER; ARTICLE; BINDING SITE; COGNITION; COGNITIVE DEFECT; CONTROLLED STUDY; CONVULSION; DEMENTIA; DRUG EFFECT; MEMORY DISORDER; NONHUMAN; OOCYTE; VOLTAGE CLAMP; XENOPUS;

ANIMALS; BICYCLO COMPOUNDS, HETEROCYCLIC; BINDING, COMPETITIVE; BIOLOGICAL AVAILABILITY; CONVULSANTS; DOGS; HUMANS; MACACA MULATTA; MICE; NOOTROPIC AGENTS; OOCYTES; PATCH-CLAMP TECHNIQUES; PHTHALAZINES; RADIOLIGAND ASSAY; RATS; RECEPTORS, GABA-A; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZOLES; XENOPUS LAEVIS;

EID: 11144356499     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm031076j     Document Type: Article

References (34)

1. A receptors: Classification on the basis of subunit structure and receptor function. Pharmacol. Rev. 1998, 50, 291-313.
2. A receptors have α5β3γ2 pharmacological characteristics. Mol. Pharmacol. 1998, 54, 928-933.
3. A receptor subtypes. Pharmacol. Rev. 1995, 47, 181-234.
4. Olsen, R. W.; Venter, J. C. Benzodiazepine/GABA Receptors and Chloride Channels: Structural and Functional Properties; Alan R. Liss Inc.: New York, 1986.
5. Cole, S. O. Effects of benzodiazepines on acquisition and performance: A critical assessment. Neurosci. Biobehav. Rev. 1986, 10, 265-272.
6. Ghoneim, M. M.; Mewaldt, S. P. Benzodiazepines and human memory: A review. Anaesthesiology 1990, 72, 926-938.
7. McNamara, R. K.; Skelton, R. W. Benzodizepine receptor antagonists flumazenil and CGS 8216 and inverse agonist β-CCM enhance spatial learning in the rat: Dissociation from anxiogenic actions. Psychobiology 1993, 21 (2), 101-108.
8. DeLorey, T. M.; Lin, R. C.; McBrady, B.; He, X.; Cook, J. M.; Lameh, J.; Loew, G. H. Influence of benzodiazepine binding site ligands on fear-conditoned contextual memory. Eur. J. Pharmacol. 2001, 426, 45-54.
9. Bailey, D. J.; Tetzlaff, J. E.; Cook, J. M.; He, X.; Helmstetter, F. J. Effects of Hippocampal Injections of a Novel Ligand Selective for the α5β2γ2 Subunits of the GABA/Benzodiazepine Receptor on Pavlovian Conditioning. Neurobiol. Learn. Mem. 2002, 78, 1-10.
10. Dorow, R.; Horowski, R.; Paschelke, G.; Amin, M.; Braestrup, C. Severe anxiety induced by FG 7142, a β-carboline ligand for benzodiazepine receptors. Lancet 1983, 2, 98-99.
11. Petersen, E. N. DMCM: A potent convulsive benzodiazepine receptor ligand. Eur. J. Pharmacol. 1983, 94, 117-124.
12. Little, H.; Nutt, D. J.; Taylor, S. C. Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling. Br. J. Pharmacol. 1984, 83, 951-958.
13. A receptor subtypes. Nature 1999, 401, 796-800.
14. Low, K.; Crestani, F.; Keist, R.; Benke, D.; Brunig, I.; Benson, J. A.; Fritschy, J.-M.; Rulicke, T.; Bluethmann, H.; Mohler, H.; Rudolph, U. Molecular and neuronal substrate for the selective attenuation of anxiety. Science 2000, 290, 131-134.
15. A receptor α1 subtype. Nat. Neurosci. 2000, 3, 587-592.
16. A receptor heterogeneity in the adult rat brain: Differential regional and cellular distribution of seven major subunits. J. Comp. Neurol. 1995, 359, 154-194.
17. A receptors in rat brain. Brain Res. 1999, 822, 265-270.
18. A Receptor. J. Neurosci. 2002, 22, 5572-5580.
19. A receptors. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 8980-8985.
20. A/BzR Subtypes (α1β3γ2, α5β3γ2, and α6β3γ2) via a Comprehensive Ligand-Mapping Approach. J. Med. Chem. 2000, 43, 71-95.
21. A/BzR sites. Med. Chem. Res. 1999, 9, 71-88.
22. Chambers, M. S.; Atack, J. R.; Bromidge, F. A.; Broughton, H. B.; Cook, S.; Dawson, G. R.; Hobbs, S. C.; Maubach, K. A.; Reeve, A. J.; Seabrook, G. R.; Wafford, K.; MacLeod, A. M. 6,7-Dihydro-2-benzothiophen-4(5H)-ones: A Novel Class of GABA-A α5 Receptor Inverse Agonists. J. Med. Chem. 2002, 45, 1176-1179.
23. Chambers, M. S.; Atack, J. R.; Broughton, H. B.; Collinson, N.; Cook, S. ; Dawson, G. R.; Hobbs, S. C.; Marshall, G.; Maubach, K.; Pillai, G. V.; Reeve, A. J.; Seabrook, G. R.; Wafford, K.; MacLeod, A. M. Identification of a Novel, Selective GABA-A α5 Receptor Inverse Agonist Which Enhances Cognition. J. Med. Chem. 2003, 46, 2227-2240.
24. Wafford, K. A.; Whiting, P. J.; Kemp, J. A. Differences in affinity and efficacy of benzodiazepine receptor ligands at recombinant γ-aminobutyric acid A receptor subtypes. Mol. Pharmacol. 1993, 43, 240-244.
25. Carling, R. W.; Moore, K. W.; Street, L. J.; Wild, D.; Isted, C.; Leeson, P. D.; Thomas, S.; O'Connor, D.; McKernan, R. M.; Quirk, K.; Cook, S. M.; Atack, J. R.; Wafford, K. A.; Thompson, S. A.; Dawson, G. R.; Ferris, P.; Castro, J. L. 3-Phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and Analogues: High-Affinity γ-Aminobutyric Acid-A Benzodiazepine Receptor Ligands with α2, α3, and α5-Subtype Selectivity over α1. J. Med. Chem. 2004, 47, 1807-1822.
26. Hollinshead, S. P.; Trudell, M. L.; Skolnick, P.; Cook, J. M. Structural Requirements for Agonist Actions at the Benzodiazepine Receptor: Studies with Analogues of 6-(Benzyloxy)-4-(methoxymethyl)-β-carboline-3-carboxylic Acid Ethyl Ester. J. Med. Chem. 1990, 33, 1062-1069.
27. Colotta, V.; Cechi, L.; Melani, F.; Filacchioni, G.; Martini, C.; Giannaccini, G.; Lucacchini, A. Tricyclic Heteroaromatic Systems. [1]Benzopyranopyrrol-4-ones and [1]Benzopyrano-1,2,3-triazol-4-ones as Benzodiazepine Receptor Ligands. Synthesis and Structure-Activity Relationships. J. Med. Chem. 1990, 33, 2646-2651.
28. Aα5 Receptor Subtype. Patent WO 98/04560, 1998.
29. Carling, W. R.; Ladduwahetty, T.; MacLeod, A. M.; Merchant, K. J.; Moore, K. W.; Sternfeld, F.; Street, L. J. Substituted 1,2,4-Triazolo[3,4-a]phthalazine Derivatives As GABA Alpha 5 Ligands. Patent WO 98/50385, 1998.
30. Roberts, A. J.; Keith, L. D. Mineralcorticoid receptors mediate the enhancing effects of corticosterone on convulsion susceptibility in mice. J. Pharmacol. Exp. Ther. 1994, 270, 505-511.
31. A receptors. Neuropsychopharmacology 1999, 20, 255-262
32. As determined in the rat elevated plus maze model for anxiety. Dawson, G. R.; Tricklebank, M. D. Trends Pharmacol. Sci. 1995, 16, 33-36.
33. 3H]Ro 15-1788 binding was used to determine occupancy of α5-containing receptors in rats. Ro 15-1788 binds with equal affinity to α1-, α2-, α3-, and α5-containing receptors, and the in vivo binding of the radioligand reflects binding to this combined receptor population. Since 16 also binds with comparable affinity to the α1, α2, α3, and α5 subtypes, the doses required to occupy α5-containing receptors are the same as those required to occupy the combined receptor population.
34. Steele, R. J.; Morris, R. G. M. Delay-dependent Impairment of a Matching-to-Place Task with Chronic and Intrahippocampal Infusion of the NMDA-Antagonist D-AP5. Hippocampus 1999, 9, 118-136.