Potent 4-aryl- or 4-arylalkyl-substituted 3-isoxazolol GABAA antagonists: Synthesis, pharmacology, and molecular modeling

Journal of Medicinal Chemistry

Volumn 48, Issue 2, 2005, Pages 427-439

  Frølund, Bente ^a   Jensen, Lars S ^a   Guandalini, Luca ^a   Canillo, Carolina ^a   Vestergaard, Henrik T ^a   Kristiansen, Uffe ^a   Nielsen, Birgitte ^a   Stensbøl, Tine B ^a   Madsen, Christian ^a   Krogsgaard Larsen, Povl ^a   Liljefors, Tommy ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

3 AMINO 2 (3 CARBOXYPROPYL) 6 (4 METHOXYPHENYL)PYRIDAZINIUM BROMIDE; 3 HYDROXY 5 (4 PIPERIDYL)ISOXAZOLE; 4 (1 NAPHTHYL) 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 (2 NAPHTHYL) 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 [(1 BROMO 2 NAPHTHYL)METHYL] 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 [(1 CHLORO 2 NAPHTHYL)METHYL] 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 [(1 CYANO 2 NAPHTHYL)METHYL] 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 [(1 FLUORO 2 NAPHTHYL)METHYL] 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 [(1 METHYLTHIO 2 NAPHTHYL)METHYL] 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 [(1 PHENYL 2 NAPHTHYL)METHYL] 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 [(1 PHENYLTHIO 2 NAPHTHYL)METHYL] 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 [(5 BROMO 2 NAPHTHYL)METHYL] 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 [(7 BROMO 2 NAPHTHYL)METHYL] 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 [(8 BROMO 2 NAPHTHYL)METHYL] 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID A RECEPTOR BLOCKING AGENT; 4 AMINOBUTYRIC ACID B RECEPTOR; 4 PHENYL 5 (4 PIPERIDYL) 3 ISOXAZOLOL HYDROBROMIDE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BRAIN NERVE CELL; CONTROLLED STUDY; DRUG EFFECT; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; ELECTROPHYSIOLOGY; MALE; MOLECULAR MODEL; MOUSE; NERVE CELL CULTURE; NONHUMAN; PATCH CLAMP; RAT; RAT STRAIN; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BINDING SITES; CELLS, CULTURED; CEREBRAL CORTEX; ISOXAZOLES; LIGANDS; MALE; MICE; MODELS, MOLECULAR; NAPHTHALENES; NEURONS; PATCH-CLAMP TECHNIQUES; PIPERIDINES; RADIOLIGAND ASSAY; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, GABA-A; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 19944433629     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049256w     Document Type: Article

References (30)

1. Chebib, M.; Johnston, G. A. R. GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology. J. Med. Chem. 2000, 43, 1427-1447.
2. Enna, S. J.; Bowery, N. G. The GABA Receptors; The Humana Press: Totowa, NJ, 1997.
3. A receptors. Brain Res. Rev. 1999, 29, 196-217.
4. Thomsen, C.; Ebert, B. Modulators of the GABA receptor. Novel therapeutic prospects. Glutamate and GABA Receptors and Transporters. Structure, Function and Pharmacology; Taylor & Francis: New York, 2002; pp 407-427.
5. Krogsgaard-Larsen, P.; Johnston, G. A. R.; Curtis, D. R.; Game, C. J. A.; McCulloch, R. M. Structure and biological activity of a series of conformationally restricted analogues of GABA. J. Neurochem. 1975, 25, 803-809.
6. Krogsgaard-Larsen, P.; Johnston, G. A. R.; Lodge, D.; Curtis, D. R. A New Class of GABA Agonist. Nature 1977, 268, 53-55.
7. Wermuth, C. G.; Bourguignon, J.-J.; Schlewer, G.; Gies, J.-P.; Schoenfelder, A.; Melikian, A.; Bouchet, M.-J.; Chantreux, D.; Molimard, J.-C.; Heaulme, M.; Chambon, J.-P.; Biziere, K. Synthesis and structure-activity relationships of a series of aminopyridazine derivatives of y-aminobutyric acid acting as selective GABA-A antagonists. J. Med. Chem. 1987, 30, 239-249.
8. A receptors. Neurochem. Int. 1999, 34, 379-385.
9. McKernan, R. M.; Whiting, P. J. Which GABAA-receptor subtypes really occur in the brain? Trends Neurosci. 1996, 19, 139-143.
10. A receptor agonists; Ph.D. Thesis, Royal Danish School of Pharmacy: Copenhagen, 2000.
11. A antagonists: design, synthesis, and pharmacology. J. Med. Chem. 2000, 43, 4930-4933.
12. A antagonists: synthesis, pharmacology and molecular modeling. J. Med. Chem. 2002, 45, 2454-2468.
13. Talukdar, S.; Hsu, J.-L.; Chou, T.-C.; Fang, J.-M. Direct transformation of aldehydes to nitriles using iodine in ammonia water. Tetrahedron Lett. 2001, 42, 1103-1105.
14. A receptors - correlation with hydrophobicity. Eur. J. Pharmacol. 2002, 451, 125-132.
15. Spartan SGI, version 5.1.1.; Irvine, CA
16. Pedersen, D. S.; Rosenbohm, C. Dry Column Vacuum Chromatography. Synthesis 2001, 2431-2434.
17. Ellingboe, J. W.; Lombardo, L. J.; Alessi, T. R.; Nguyen, T. T.; Guzzo, F.; Guinosso, C. J.; Bullington, J.; Browne, E. N.; Bagli, J. F.; Wrenn, J.; et al. Antihyperglycemic activity of novel naphthalenyl 3H-1,2,3,5-oxathiadiazole 2-oxides. J. Med. Chem. 1993, 36, 2485-2493.
18. Terfort, A.; Görls, H.; Brunner, H. The First Helical-Chiral Phosphane Ligands: rac-[5]- and rac-[6]-Heliphos. Synthesis 1997, 79-86.
19. Viala, J.; Santelli, M. Three-carbon homologating agent: new preparation of (3,3-diisopropoxypropyl)triphenylphosphonium bromide. Synthesis 1988, 395-397.
20. Newman, M. S.; Dhawab, B.; Kumar, S. Abnormal products in the Siegrist reation involving ortho-fluorinated intermediates. J. Org. Chem. 1978, 43, 524-525.
21. Blum, J.; Grauer, F.; E. D., B. The synthesis of 12-fluoro-7-methyl- and 7-fluoro-benz[a]anthracene: a contribution to the study of photocylization. Tetrahedron 1969, 25, 3501-3507.
22. Clayden, J.; C., M.; Westlund, N.; Frampton, C. S. Atroposelective attack of nucleophiles on 2-formyl-1-naphthamides and their derivatives: chelation and nonchelation control. J. Chem. Soc., Perkin Trans. 1 2000, 1363-1378.
23. Byberg, J. R.; Labouta, I. M.; Falch, E.; Hjeds, H.; Krogsgaard-Larsen, P.; Curtis, D. R.; Gynther, B. D. Synthesis and biological activity of a GABA-A agonist which has no effect on benzodiazepine binding and structurally related glycine antagonists. Drug Des. Delivery 1987, 1, 261-274.
24. Herts, E.; Yu, A. C. H.; Hertz, L.; Juurlink, B. H. J.; Schousboe, A. Preparation of primary cultures of mouse cortical neurons. In A Dissection and Tissue Culture Manual of the Nervous System; Alan R. Liss Inc.: New York, 1989.
25. Hamill, O. P.; Marty, A.; Neher, E.; Sakmann, B.; Sigworth, F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membranes. Pflügers Arch. 1981, 391, 85-100.
26. Carbone, E.; Lux, H. D. Kinetics and selectivity of a low-voltage-activated calcium current in chick and rat sensory neurones. J. Physiol. 1987, 386, 547-570.
27. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. MacroModel - An integrated software system for modeling organic and bioorganic molecules using molecular mechanics. J. Comput. Chem. 1990, 11, 440-467.
28. Chang, G.; Guida, W. C.; Still, W. C. An internal coordinate Monte Carlo method for searching conformational space. J. Am. Chem. Soc. 1989, 111, 4379-4386.
29. Still, W. C.; Tempczyk, A.; Hawley, R. C.; Hendrickson, T. Semianalytical treatment of solvation for molecular mechanics and dynamics. J. Am. Chem. Soc. 1990, 112, 6127-6129.
30. Christopoulos, A. Assessing the distribution of parameters in models of ligand-receptor interaction: to log or not to log. Trends Pharmacol. Sci. 1998, 19, 351-357.