Selective inhibitors of glial GABA uptake: Synthesis, absolute stereochemistry, and pharmacology of the enantiomers of 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole (exo-THPO) and analogues

Journal of Medicinal Chemistry

Volumn 42, Issue 26, 1999, Pages 5402-5414

  Falch, Erik ^a   Perregaard, Jens ^b   Frølund, Bente ^a   Søkilde, Birgitte ^a   Buur, Anders ^b   Hansen, Lene M ^a   Frydenvang, Karla ^a   Brehm, Lotte ^a   Bolvig, Tina ^a   Larsson, Orla M ^a   Sanchez, Connie ^b   White, Harold S ^c   Schousboe, Arne ^a   Krogsgaard Larsen, Povl ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b H LUNDBECK A S   (Denmark)

^c UNIVERSITY OF UTAH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID RECEPTOR BLOCKING AGENT; BENZAMIDE DERIVATIVE; ISOTHIAZOLE DERIVATIVE; ISOXAZOLE DERIVATIVE; NIPECOTIC ACID; PRODRUG;

4 AMINOBUTYRIC ACID UPTAKE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICONVULSANT ACTIVITY; ARTICLE; CHEMICAL REACTION; DIASTEREOISOMER; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; MOUSE; NONHUMAN; STEREOCHEMISTRY;

ANIMALS; CRYSTALLOGRAPHY, X-RAY; GAMMA-AMINOBUTYRIC ACID; HYDROGEN BONDING; ISOXAZOLES; MAGNETIC RESONANCE SPECTROSCOPY; MICE; MOLECULAR STRUCTURE; NEUROGLIA; RATS; STEREOISOMERISM;

EID: 0033619981     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9904452     Document Type: Article

References (51)

1. Morselli, P. L., Löscher, W., Lloyd, K. G., Meldrum, B., Reynolds, E. H., Eds. Neurotransmitters, Seizures, and Epilepsy; Raven Press: New York, 1981.
2. Fariello, R. G., Morselli, P. L., Lloyd, K. G., Quesney, L. F., Engel, J., Eds. Neurotransmitters, Seizures, and Epilepsy II; Raven Press: New York, 1984.
3. Nistico, G., Morselli, P. L., Lloyd, K. G., Fariello, R. G., Engel, J., Eds. Neurotransmitters, Seizures, and Epilepsy III; Raven Press: New York, 1986.
4. Meldrum, B. S. Epilepsy and γ-aminobutyric acid-mediated inhibition. Int. Rev. Neurobiol. 1975, 17, 1-36.
5. Meldrum, B. S. Pharmacology of GABA. Clin. Neuropharmacol. 1982, 5, 293-316.
6. Bowery, N. G., Nistico, G., Eds. GABA: Basic Research and Clinical Applications; Pythagora Press: Rome, 1989.
7. Nanavati, S. M.; Silverman, R. B. Design of potential anticonvulsant agents: mechanistic classification of GABA aminotransferase inactivators. J. Med. Chem. 1989, 32, 2413-2421.
8. Schechter, P. J. Clinical pharmacology of vigabatrin. Br. J. Clin. Pharmacol. 1989, 27, 19S-22S.
9. Yunger, L. M.; Fowler, P. J.; Zarevics, P.; Setler, P. E. Novel inhibitors of γ-aminobutyric acid (GABA) uptake: anticonvulsant actions in rats and mice. J. Pharmacol. Exp. Ther. 1984, 228, 109-115.
10. Andersen, K. E.; Braestrup, C.; Grønwald, F. C.; Jørgensen, A. S.; Nielsen, E. B.; Sonnewald, U.; Sørensen, P. O.; Suzdak, P. D.; Knutsen, L. J. S. The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidate. J. Med. Chem. 1993, 36, 1716-1725.
11. Krogsgaard-Larsen, P.; Johnston, G. A. R. Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isoxazoles and related compounds. J. Neurochem. 1975, 25, 797-802.
12. Johnston, G. A. R.; Krogsgaard-Larsen, P.; Stephanson, A. Betel nut constituents as inhibitors of γ-aminobutyric acid uptake. Nature (London) 1975, 258, 627-628.
13. Krogsgaard-Larsen, P.; Johnston, G. A. R. Structure-activity studies on the inhibition of GABA binding to rat brain membranes by muscimol and related compounds. J. Neurochem. 1978, 30, 1377-1382.
14. Krogsgaard-Larsen, P.; Thyssen, K.; Schaumburg, K. Inhibitors of GABA uptake. Syntheses and proton NMR spectroscopic investigations of guvacine, (3RS,4SR)-4-hydroxypiperidine-3-carboxylic acid, and related compounds. Acta Chem. Scand., Ser. 8 1978, B32, 327-334.
15. Larsson, O. M.; Falch, E.; Schousboe, A.; Krogsgaard-Larsen, P. GABA uptake inhibitors: kinetics and molecular pharmacology. Adv. Biosci. (Oxford) 1991, 82, 197-200.
16. Johnston, G. A. R.; Stephanson, A. L.; Twitchin, B. Uptake and release of nipecotic acid by rat brain slices. J. Neurochem. 1976, 26, 83-87.
17. Larsson, O. M.; Krogsgaard-Larsen, P.; Schousboe, A. Characterization of the uptake of GABA, nipecotic acid and cis-4-hydroxynipecotic acid in cultured neurons and astrocytes. Neurochem. Int. 1985, 7, 853-860.
18. Larsson, O. M.; Krogsgaard-Larsen, P.; Schousboe, A. High-affinity uptake of (RS)-nipecotic acid in astrocytes cultured from mouse brain. Comparison with GABA transport. J. Neurochem. 1980, 34, 970-977.
19. Schousboe, A.; Thorbek, P.; Hertz, L.; Krogsgaard-Larsen, P. Effects of GABA analogues of restricted conformation on GABA transport in astrocytes and brain cortex slices and on GABA receptor binding. J. Neurochem. 1979, 33, 181-189.
20. Juhász, G.; Kékesi, K. A.; Nyitrai, G.; Dobolyi, A.; Krogsgaard-Larsen, P.; Schousboe, A. Differential effects of nipecotic acid and 4,5,6,7-tetrahydro-isoxazolo[4,5-c]pyridin-3-ol on extracellular γ-aminobutyrate levels in rat thalamus. Eur. J. Pharmacol. 1997, 331, 139-144.
21. Gonsalves, S. F.; Twitchell, B.; Harbaugh, R. E.; Krogsgaard-Larsen, P.; Schouaboe, A. Anticonvulsant activity of intracerebroventricularly administered glial GABA uptake inhibitors and other GABA mimetics in chemical seizure models. Epilepsy Res. 1989, 4, 34-41.
22. Krogsgaard-Larsen, P.; Falch, E.; Larsson, O. M.; Schousboe, A. GABA uptake inhibitors: relevance to antiepileptic drug research. Epilepsy Res. 1987, 1, 77-93.
23. Falch, E.; Larsson, O. M.; Schousboe, A.; Krogsgaard-Larsen, P. GABA-A agonists and GABA uptake inhibitors: structure-activity relationships. Drug Dev. Res. 1990, 21, 169-188.
24. Johnson, C. K. ORTEP II. A Fortran Thermal-Ellipsoid Plot Programme for Crystal Structure Illustrations; Report ORNL-5138; Oak Ridge National Laboratory: Oak Ridge, TN, 1976.
25. Flack, H. D. On enantiomorph-polarity estimation. Acta Crystallogr. 1983, A39, 876-881.
26. Sheldrick, G. M. SHELXL97. Program for Crystal Structure Refinement; University of Göttingen: Göttingen, Germany, 1997.
27. Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen, A. G.; Taylor, R. Typical interatomic distances: organic compounds. In International Tables for Crystallography; Wilson, A. J. C., Ed.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1995; Vol. C, pp 685-706.
28. Spek, A. L. PLATON, an integrated tool for the analysis of the results of a single-crystal structure determination. Acta Crystallogr. 1990, A46, C34.
29. 50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
30. Krogsgaard-Larsen, P.; Nielsen, L.; Falch, E.; Curtis, D. R. GABA agonists. Resolution, absolute stereochemistry, and enantioselectivity of (S)-(+)- and (R)-(-)-dihydromuscimol. J. Med. Chem. 1986, 28, 1612-1617.
31. Johnston, G. A. R.; Krogsgaard-Larsen, P.; Stephanson, A. L.; Twitchin, B. Inhibition of the uptake of GABA and related amino acids in rat brain slices by the optical isomers of nipecotic acid. J. Neurochem. 1976, 26, 1029-1032.
32. Schousboe, A.; Larsson, O. M.; Hertz, L.; Krogsgaard-Larsen, P. Heterocyclic GABA analogues as new selective inhibitors of astroglial GABA transport. Drug Dev. Res. 1981, 1, 115-127.
33. Christensen, A. V.; Larsen, J.-J. Antinociceptive and anticonvulsive effect of THIP, a pure GABA agonist. Pol. J. Pharmacol. Pharm. 1982, 34, 127-134.
34. Wood, J. D.; Johnson, D. D.; Krogsgaard-Larsen, P.; Schousboe, A. Anticonvulsant activity of the glial-selective GABA uptake inhibitor, THPO. Neuropharmacology 1983, 22, 139-142.
35. White, H. S.; Wolf, H. H.; Swinyard, E. A.; Skeen, G. A.; Sofia, R. D. A neuropharmacological evaluation of felbamate as a novel anticonvulsant. Epilepsia 1992, 33, 564-572.
36. Johnston, G. A. R.; Krogsgaard-Larsen, P.; Stephanson, A. L.; Twitchin, B. Inhibition of the uptake of GABA and related amino acids in rat brain slices by the optical isomers of nipecotic acid. J. Neurochem. 1976, 26, 1029-1032.
37. Knutsen, L. J. S.; Andersen, K. E.; Lau, J.; Lundt, B. F.; Henry, R. F.; Morton, H. E.; Nærum, L.; Petersen, H.; Stephensen, H.; Suzdak, P. D.; Swedberg, M. D. B.; Thomsen, C.; Sørensen, P. O. Synthesis of novel GABA uptake inhibitors. 3. Diaryloxime and diarylvinyl ether derivatives of nipecotic acid and guvacine as anticonvulsant agents. J. Med. Chem. 1999, 42, 3447-3462.
38. Larsson, O. M.; Falch, E.; Krogsgaard-Larsen, P.; Schousboe, A. Kinetic characterization of inhibition of GABA uptake into cultured neurons and astrocytes by 4,4-diphenyl-3-butenyl derivatives of nipecotic acid and guvacine. J. Neurochem. 1988, 50, 818-823.
39. Jacquier, R.; Petrus, C.; Petrus, F.; Verducci, J. Étude dans la serie des azoles. LXII.-Synthèse univoque d'isoxazolones-3. Étude de leur tautomeric. Bull. Soc. Chim. Fr. 1970, 5, 1978-1985.
40. Drewes, H. R. Process for the preparation of cyclohexanone-2-carboxamide. U.S. 4169952 to du Pont de Nemours; Chem. Abstr. 1979, 92, P 22150a.
41. Enraf-Nonius. CAD-4 Software, version 5.0; Enraf-Nonius: Delft, The Netherlands, 1989.
42. Blessing, R. H. Data reduction and error analysis for accurate single-crystal diffraction intensities. Crystallogr. Rev. 1987, 1, 3-58.
43. Blessing, R. H. DREADD - data reduction and error analysis for single-crystal diffractometer data. J. Appl. Crystallogr. 1989, 22, 396-397.
44. DeTitta, G. T. ABSORB: An absorption correction programme for crystals enclosed in capillaries with trapped mother liquor. J. Appl. Crystallogr. 1985, 18, 75-79.
45. Sheldrick, G. M. SHELXS97. Program for the Solution of Crystal Structures; University of Göttingen: Göttingen, Germany, 1997.
46. Sheldrick, G. M. Phase annealing in SHELX-90: Direct methods for larger structures. Acta Crystallogr. 1990, A46, 467-473.
47. International Tables for Crystallography; Wilson, A. J. C., Ed.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1995; Vol. C, Tables 4.2.6.8 and 6.1.1.4.
48. Main, P.; Fiske, S. J.; Hull, S. E.; Lessinger, L.; Germain, G.; Declercq, J.-P.; Woolfson, M. M. MULTAN11/82. A System of Computer Programs for the Automatic Solution of Crystal Structures from X-ray Diffraction Data; Universities of York: England, and Lovain: Belgium, 1982.
49. Frenz, B. A.; Associates Inc. SDP Structure Determination Package; College Station: Texas, and Enraf-Nonius: Delft, The Netherlands, 1985.
50. Sheldrick, G. M. SHELXL93. Program for Crystal Structure Refinement; University of Göttingen: Göttingen, Germany, 1993.
51. 3H]GABA into rat brain synaptosomes. Acta Pharmacol. Toxicol. 1987, 42, 73-76.