Probing the orthosteric binding site of GABAa receptors with heterocyclic GABA carboxylic acid bioisosteres

Neurochemical Research

Volumn 39, Issue 6, 2014, Pages 1005-1015

  Petersen, Jette G ^a   Bergmann, Rikke ^a   Krogsgaard Larsen, Povl ^a   Balle, Thomas ^b   Frløund, Bente ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY OF SYDNEY   (Australia)

Author keywords

GABA; Heterocyclic carboxylic acid bioisosteres; Structural models; Structure activity studies

Indexed keywords

3 HYDROXYISOTHIAZOLE; 3 HYDROXYISOXAZOLE; 3 HYDROXYISOXAZOLINE; 4 AMINOBUTYRIC ACID A RECEPTOR; HETEROCYCLIC CARBOXYLIC ACID; ISOXAZOLE DERIVATIVE; LIGAND; MUSCIMOL; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID; CARBOXYLIC ACID; HETEROCYCLIC COMPOUND; PROTEIN BINDING;

BINDING SITE; HUMAN; MOLECULAR PROBE; NONHUMAN; ORTHOSTERIC BINDING SITE; PHARMACOPHORE; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; REVIEW; STRUCTURE ACTIVITY RELATION; SYNTHESIS; ANIMAL; CHEMISTRY; METABOLISM; PHYSIOLOGY;

ANIMALS; BINDING SITES; CARBOXYLIC ACIDS; GAMMA-AMINOBUTYRIC ACID; HETEROCYCLIC COMPOUNDS; HUMANS; PROTEIN BINDING; RECEPTORS, GABA-A; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84901467465     PISSN: 03643190     EISSN: 15736903     Source Type: Journal    
DOI: 10.1007/s11064-013-1226-6     Document Type: Review

References (66)

1. Foster AC, Kemp JA (2006) Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol 6(1):7-17 (Pubitemid 43103814)
2. Johnston GAR (2005) GABAA receptor channel pharmacology. Curr Pharm Des 11(15):1867
3. Dougherty DA (2008) Cys-loop neuroreceptors: structure to the rescue? Chem Rev 108(5):1642-1653
4. Davies PA, Wang W, Hales TG, Kirkness EF (2003) A novel class of ligand-gated ion channel is activated by Zn2+. J Biol Chem 278(2):712-717 (Pubitemid 36790740)
5. Sieghart W (2006) Structure, pharmacology, and function of GABAA receptor subtypes. In: Enna SJ (ed) Advances in pharmacology, vol 54. Academic Press, California, pp 231-263
6. Karlin A (2002) Emerging structure of the nicotinic acetylcholine receptors. Nat Rev Neurosci 3(2):102-114
7. Paul JW (2003) GABAA receptor subtypes in the brain: a paradigm for CNS drug discovery? Drug Discov Today 8(10):445-450
8. Johnston GAR, Curtis DR, de Groat WC, Duggan AW (1968) Central actions of ibotenic acid and muscimol. Biochem Pharmacol 17(12):2488-2489
9. Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA (1997) Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human γ-aminobutyric acid type a receptors. Mol Pharmacol 52(6):1150-1156 (Pubitemid 28013735)
10. Krogsgaard-Larsen P, Johnston GAR, Lodge D, Curtis DR (1977) A new class of GABA agonist. Nature 268(5615):5355
11. Byberg JR, Labouta IM, Falch E, Hjeds H, Krogsgaard-Larsen P (1987) Synthesis and biological activity of a GABAA agonist which has no effect on benzodiazepine binding and of structurally related glycine antagonists. Drug Des Deliv 1:261-274 (Pubitemid 18065560)
12. Frølund B, Tagmose L, Liljefors T, Stensbøll TB, Engblom C, Kristiansen U, Krogsgaard-Larsen P (2000) A novel class of potent 3-isoxazolol GABAA antagonists: design, synthesis, and pharmacology. J Med Chem 43(26):4930-4933 (Pubitemid 32039015)
13. Frølund B, Jørgensen AT, Tagmose L, Stensbøl TB, Vestergaard HT, Engblom C, Kristiansen U, Sanchez C, Krogsgaard-Larsen P, Liljefors T (2002) Novel Class of potent 4-arylalkyl substituted 3-isoxazolol GABAA antagonists: synthesis, pharmacology, and molecular modeling. J Med Chem 45(12):2454-2468 (Pubitemid 34595215)
14. Jacobsen P, Labouta IM, Schaumburg K, Falch E, Krogsgaard-Larsen P (1982) Hydroxy- and amino-substituted piperidine-carboxylic acids as γ-aminobutyric acid agonists and uptake inhibitors. J Med Chem 25(10):1157-1162 (Pubitemid 13241899)
15. Krogsgaard-Larsen P, Larsen ALN, Thyssen K (1978) GABA receptor agonists. synthesis of muscimol analogues including (R)-and (S)-5-(1-aminoethyl)-3- isoxazolol and (RS)-5-aminomethyl-2-isoxazolin-3-ol. Acta Chem Scand B32:469-477 (Pubitemid 9098231)
16. Krogsgaard-Larsen P, Hjeds H, Curtis DR, Lodge D, Johnston GAR (1979) Dihydromuscimol, thiomuscimol, and related heterocyclic compounds as GABA analogues. J Neurochem 32(6):1717-1724 (Pubitemid 9195167)
17. Petersen JG, Bergmann R, Møller HA, Jørgensen CG, Nielsen B, Kehler J, Frydenvang K, Kristensen J, Balle T, Jensen AA, Kristiansen U, Frølund B (2013) Synthesis and biological evaluation of 4-(aminomethyl)-1-hydroxypyrazole analogues of muscimol as γ-aminobutyric acid(a) receptor agonists. J Med Chem 56(3):993-1006
18. Pevarello P, Varasi M (1992) An improved synthesis of muscimol. Synth Commun 22(13):1939-1948
19. Gagneux AR, Häfliger F, Eugster CH, Good R (1965) Synthesis of pantherine (agarin). Tetrahedron Lett 6(25):2077-2079
20. Loev B, Wilson JW, Goodman MM (1970) Synthesis of compounds related to muscimol (pantherine, agarin). J Med Chem 13(4):738-741
21. McCarry BE, Savard M (1981) A facile synthesis of muscimol. Tetrahedron Lett 22(51):5153-5156 (Pubitemid 12220703)
22. Jäger V (1982) Frey M (1982) A short synthesis of muscimol. Liebigs Ann Chem 4:817-820
23. Welch WM (1982) A shorter synthesis of muscimol. Synth Commun 12(14):1089-1092
24. Oster TA, Harris TM (1983) Generation and reactions of the dianion of 3-hydroxy-5-methylisoxazole, a convenient β-keto amide synthon. total synthesis of muscimol. J Org Chem 48(23):4307-4311 (Pubitemid 14185239)
25. Frey M, Jäger V (1985) Synthesis of N-substituted muscimol derivatives including N-glycylmuscimol. Synthesis 12:1100-1104
26. Chiarino D, Napoletano M, Sala A (1986) A convenient synthesis of muscimol by a 1,3-dipolar cycloaddition reaction. Tetrahedron Lett 27(27):3181-3182 (Pubitemid 16039787)
27. Nakamura N, Tajima Y, Sakai K (1982) Direct phenylation of isoxazoles using palladium catalysts. Synthesis of 4-phenylmuscimol. Heterocycles 17(1):235-245
28. Hjeds H, Christensen IT, Cornett C, Frølund B, Falch E, Pedersen JB, Krogsgaard-Larsen P (1992) 3-Hydroxyisoxazole bioisosteres of GABA. Synthesis of a series of 4-substituted muscimol analogues and identification of a bicyclic 2-isoxazoline rearrangement product. Acta Chem Scand 46:772-777
29. Bowden K, Crank G, Ross WJ (1968) The synthesis of pantherine and related compounds. J Chem Soc C 172-185
30. De Amici M, De Micheli C, Misani V (1990) Nitrile oxides in medicinal chemistry-2. Synthesis of the two enantiomers of dihydromuscimol. Tetrahedron 46(6):1975-1986 (Pubitemid 20214691)
31. Caldirola P, De Amici M, De Micheli C (1986) An easy synthesis of dihydromuscimol. Tetrahedron Lett 27(38):4651-4652 (Pubitemid 16012983)
32. Krogsgaard-Larsen P, Nielsen L, Falch E, Curtis DR (1985) GABA agonists. Resolution, absolute stereochemistry and enantioselectivity of (S)-(+)- and (R)-(-)-dihydromuscimol. J Med Chem 28(11):1612-1617 (Pubitemid 16204825)
33. Castelhano AL, Billedeau R, Pliura DH, Bonaventura BJ, Krantz A (1988) Synthesis, chemistry, and absolute configuration of novel transglutaminase inhibitors containing a 3-halo-4, 5-dihydroisoxazole. Bioorg Chem 16(3):335-340
34. Krogsgaard-Larsen P, Johnston GAR, Curtis DR, Game CJA, McCulloch RM (1975) Structure and biological activity of a series of conformationally restricted analogues of GABA. J Neurochem 25(6):803-809
35. Lykkeberg J, Krogsgaard-Larsen P (1976) Structural analogues of GABA. Synthesis of 5-aminomethyl-3-isothiazolol (thiomuscimol). Acta Chem Scand Ser B 30:781-785
36. Lykkeberg J (1978) Synthesis of some pyrazol-5-ols related to muscimol. Acta Chem Scand Ser B 32:56-60
37. Hjeds H, Krogsgaard-Larsen P (1979) Muscimol analogues. synthesis of isomuscimol (3-aminomethyl-5-isoxazol) and some derivatives of azamuscimol (5-aminomethyl-2-pyrazolol). Acta Chem Scand Ser B 33:294-298
38. Ebert B, Wafford KA, Whiting PJ, Krogsgaard-Larsen P, Kemp JA (1994) Molecular pharmacology of gamma-aminobutyric acid type a receptor agonists and partial agonists in oocytes injected with different alpha, beta, and gamma receptor subunit combinations. Mol Pharmacol 46(5):957-963 (Pubitemid 24364111)
39. Høstgaard-Jensen K, O'Connor R, Dalby N, Simonsen C, Finger B, Golubeva A, Hammer H, Bergmann M, Kristiansen U, Krogsgaard-Larsen P, Bräuner-Osborne H, Ebert B, Frølund B, Cryan J, Jensen AA (2013) The orthosteric GABAA receptor ligand thio-4-PIOL displays distinctly different functional properties at synaptic and extrasynaptic receptors. Br J Pharmacol 170(4):919-932
40. Krogsgaard-Larsen P, JohnstonGA(1978) Structure-activity studies on the inhibition of GABA binding to rat brain membranes by muscimol and related compounds. J Neurochem 30(6):1377-1382 (Pubitemid 8377482)
41. Krogsgaard-Larsen P, Johnston GA, Curtis DR, Game CJ, McCulloch RM (1975) Structure and biological activity of a series of conformationally restricted analogues of GABA. J Neurochem 25(6):803-809
42. Krogsgaard-Larsen P, Johnston GA, Lodge D, Curtis DR (1977) A new class of GABA agonist. Nature 268(5615):53-55 (Pubitemid 8136628)
43. Brown N, Kerby J, Bonnert TP, Whiting PJ, Wafford KA (2002) Pharmacological characterization of a novel cell line expressing human a 4b3d GABAA receptors. Br J Pharmacol 136(7):965-974
44. Byberg JR, Labouta IM, Falch E, Hjeds H, Krogsgaard-Larsen P, Curtis DR, Gynther BD (1987) Synthesis and biological activity of a GABAA agonist which has no effect on benzodiazepine binding and of structurally related glycine antagonists. Drug Des Deliv 1(4):261-274 (Pubitemid 18065560)
45. Krehan D, í Storustovu S, Liljefors T, Ebert B, Nielsen B, Krogsgaard-Larsen P, Frølund B (2006) Potent 4-arylalkyl-substituted 3-isothiazolol GABAA competitive/noncompetitive antagonists: synthesis and pharmacology. J Med Chem 49(4):1388-1396
46. Møller HA, Sander T, Kristensen JL, Nielsen B, Krall J, Bergmann ML, Christiansen B, Balle T, Jensen AA, Frølund B (2010) Novel 4-(piperidin-4-yl)-1-hydroxypyrazoles as γ-aminobutyric acid(A) receptor ligands: synthesis, pharmacology, and structure-activity relationships. J Med Chem 53(8):3417-3421
47. Conti P, De Amici M, Pinto A, Tamborini L, Grazioso G, Frølund B, Nielsen B, Thomsen C, Ebert B (2006) De Micheli C (2006) synthesis of 3-hydroxy- and 3-carboxy-δ2-isoxazoline amino acids and evaluation of their interaction with GABA receptors and transporters. Eur J Org Chem 24:5533-5542
48. Berezhnoy D, Gibbs TT, Farb DH (2009) Docking of 1,4-benzodiazepines in the α1/γ2 GABAA receptor modulator site. Mol Pharmacol 76(2):440-450
49. Cromer BA, Morton CJ, Parker MW (2002) Anxiety over GABA(A) receptor structure relieved by AChBP. Trends Biochem Sci 27(6):280-287 (Pubitemid 34628667)
50. Ci SQ, Ren TR, Ma CX, Su ZG (2007) Modeling of alphak/gamma2 (k = 1, 2, 3 and 5) interface of GABA a receptor and docking studies with zolpidem: implications for selectivity. J Mol Graph Model 26(2):537-545
51. Sancar F, Ericksen SS, Kucken AM, Teissere JA, Czajkowski C (2007) Structural determinants for high-affinity zolpidem binding to GABA-A receptors. Mol Pharmacol 71(1):38-46 (Pubitemid 46020976)
52. O'Mara M, Cromer B, Parker M, Chung S-H (2005) Homology model of the GABAA receptor examined using brownian dynamics. Biophys J 88(5):3286-3299 (Pubitemid 40586580)
53. Trudell JR (2002) Unique assignment of inter-subunit association in GABAA α1β3γ2 receptors determined by molecular modeling. Biochim Biophys Acta Biomembr 1565(1):91-96
54. Ernst M, Bruckner S, Boresch S, Sieghart W (2005) Comparative models of GABAA receptor extracellular and transmembrane domains: important insights in pharmacology and function. Mol Pharmacol 68(5):1291-1300 (Pubitemid 41539985)
55. Padgett CL, Hanek AP, Lester HA, Dougherty DA, Lummis SCR (2007) Unnatural amino acid mutagenesis of the GABAA receptor binding site residues reveals a novel cation-π interaction between GABA and β2Tyr97. J Neurosci 27(4):886-892 (Pubitemid 46174509)
56. Mokrab Y, Bavro VN, Mizuguchi K, Todorov NP, Martin IL, Dunn SMJ, Chan SL, Chau PL (2007) Exploring ligand recognition and ion flow in comparative models of the human GABA type A receptor. J Mol Graphics Modell 26(4):760-774 (Pubitemid 47628844)
57. Chupakhin V, Palyulin V, Zefirov N (2006) Modeling the open and closed forms of GABAA receptor: analysis of ligand-receptor interactions for the GABA-binding site. Dokl Biochem Biophys 408(1):169-174 (Pubitemid 43988419)
58. Jansen M, Rabe H, Strehle A, Dieler S, Debus F, Dannhardt G, Akabas MH, Lüddens H (2008) Synthesis of GABAA receptor agonists and evaluation of their a-subunit selectivity and orientation in the GABA binding Site. J Med Chem 51(15):4430-4448
59. Law RJ, Lightstone FC (2009) Modeling neuronal nicotinic and GABA receptors: important interface salt-links and protein dynamics. Biophys J 97(6):1586-1594
60. Sander T, Frølund B, Bruun AT, Ivanov I, McCammon JA, Balle T (2011) New insights into the GABAA receptor structure and orthosteric ligand binding: receptor modeling guided by experimental data. Proteins 79(5):1458-1477
61. Hibbs RE, Gouaux E (2011) Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474(7349):54-60
62. Bergmann R, Kongsbak K, Sørensen PL, Sander T, Balle T (2013) A Unified model of the GABAA receptor comprising agonist and benzodiazepine binding sites. PLoS ONE 8(1):e52323
63. Hilf RJC, Dutzler R (2008) X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature 452(7185):375-379 (Pubitemid 351430790)
64. Celie PH, van Rossum-Fikkert SE, van Dijk WJ, Brejc K, Smit AB, Sixma TK (2004) Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 41(6):907-914 (Pubitemid 38429734)
65. Rohde LA, Ahring PK, Jensen ML, Nielsen EO, Peters D, Helgstrand C, Krintel C, Harpsoe K, Gajhede M, Kastrup JS, Balle T (2012) Intersubunit bridge formation governs agonist efficacy at nicotinic acetylcholine α4β2 receptors. J Biol Chem 287(6):4248-4259
66. Atack JR (2008) GABAA receptor subtype-selective efficacy: tpa023, an α2/α3 selective non-sedating anxiolytic and α5ia, an α5 selective cognition enhancer. CNS Neurosci Ther 14(1):25-35