Novel GABAB receptor positive modulators: A patent survey

Expert Opinion on Therapeutic Patents

Volumn 20, Issue 8, 2010, Pages 1007-1017

  Froestl, Wolfgang ^a  

^a AC IMMUNE SA   (Switzerland)

Author keywords

Agonists; Allosteric binding site; Desensitization; GABAB receptors; Orthosteric binding site; Positive allosteric modulators

Indexed keywords

2,6 DI TERT BUTYL 4 (3 HYDROXY 2,2 DIMETHYLPROPYL)PHENOL; 4 AMINOBUTYRIC ACID B RECEPTOR; 4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; ADX 48621; ADX 63365; ADX 71149; ADX 71943; BACLOFEN; CGP 13501; CGP 44532; LEVODOPA; N,N' DICYCLOPENTYL 2 METHYLTHIO 5 NITRO 4,6 PYRIMIDINEDIAMINE; NVPBHF 177; NVPBIK 834; NVPBIK 877; NVPBIK 998; UNCLASSIFIED DRUG; WO 2006 001750; WO 2007 073296; WO 2007 073297; WO 2007 073298; WO 2007 073299; WO 2007 073300; WO 2008 130313; WO 2008 130314; WO 2009 041904; WO 2009 041905; BENZODIAZEPINE RECEPTOR AFFECTING AGENT;

BONE PAIN; CHRONIC PAIN; CLINICAL TRIAL; DEPRESSION; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DYSKINESIA; GASTROESOPHAGEAL REFLUX; HUMAN; IRRITABLE COLON; NONHUMAN; REVIEW; SCHIZOPHRENIA; SKIN INFLAMMATION; WITHDRAWAL SYNDROME; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; DRUG EFFECT; DRUG INDUSTRY; PATENT; STRUCTURE ACTIVITY RELATION;

ANIMALS; DRUG DESIGN; DRUG INDUSTRY; GABA MODULATORS; HUMANS; MOLECULAR STRUCTURE; PATENTS AS TOPIC; RECEPTORS, GABA-B; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77954892234     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543776.2010.506480     Document Type: Review

References (60)

1. Urwyler S, Gjoni T, Koljatic J, et al. Mechanisms of allosteric modulation at GABA-B receptors by CGP7930 and GS39783: effects on affinities and efficacies of orthosteric ligands with distinct intrinsic properties. Neuropharmacology 2005;48:343-353
2. Couve A, Calver AR, Fairfax B, et al. Unravelling the unusual signalling properties of the GABA-B receptor. Biochem Pharmacol 2004;68:1527-1536
3. Urwyler S, Mosbacher J, Lingenhoehl K, et al. Positive allosteric modulation of native and recombinant GABA-B receptors by 2,6-di-tert.-butyl-4- (3-hydroxy-2,2-di-methyl-propyl)-phenol (CGP7930) and its aldehyde analogue CGP13501. Mol Pharmacol 2001;60:963-971
4. Urwyler S. Allosteric modulation of GABA-B receptors. In: Bowery NG, editor, Allosteric receptor modulation in drug targeting. Informa Healthcare (Taylor and Francis), New York; 2006. p. 235-258
5. Binet V, Brajon C, Le Corre L, et al. The heptahelical domain of GABAB-2 is activated directly by CGP7930, a positive allosteric modulator of the GABA-B receptor. J Biol Chem 2004;279:29085-29091
6. Schwartz TW, Holst B. Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors. J Recept Signal Transduct Res 2006;26:107-128
7. Schwartz TW, Holst B. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act? Trends Pharmacol Sci 2007;28:366-373
8. De Amici M, Dallanoce C, Holzgrabe U, et al. Allosteric ligands for G protein-coupled receptors: a novel strategy with attractive therapeutic opportunities. Med Res Rev 2010;30:463-549
9. Pin JP, Prezeau L. Allosteric modulators of GABA-B receptors: mechanism of action and therapeutic perspective. Curr Neuropharmacol 2007;5:195-201
10. Frankowska M, Filip M, Przegalinski E. Effects of GABA-B receptor ligands in animal tests of depression and anxiety. Pharmacol Rep 2007;59:645-655
11. Jacobson LH, Cryan JF. Evaluation of the anxiolytic-like profile of the GABA-B receptor positive modulator CGP7930 in rodents. Neuropharmacology 2008;54:854-862
12. Adams CL, Lawrence AJ. CGP7930: a positive allosteric modulator of the GABA-B receptor. CNS Drug Rev 2007;13:308-316
13. Urwyler S, Pozza MF, Lingenhoehl K, et al. N,N'-Dicyclopentyl-2- methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) and structurally related compounds: novel allosteric enhancers of gamma-aminobutyric acid B receptor function. J Pharmacol Exp Ther 2003;307:322-330
14. Cryan JF, Kelly PH, Chaperon F, et al. Behavioral characterization of the novel GABA-B receptor-positive modulator GS39783 (N,N'-dicyclopentyl-2- methylsulfanyl-5-nitro-pyrimidine-4,6-diamine): anxiolytic-like activity without side effects associated with baclofen or benzodiazepines. J Pharmacol Exp Ther 2004;310:952-963
15. Mombereau C, Kaupmann K, Froestl W, et al. Genetic and pharmacological evidence of a role for GABA-B receptors in the modulation of anxiety-and antidepressant-like behavior. Neuropsychopharmacology 2004;29:1050-1062
16. Wieronska JM, Wabno J, Froestl W, et al. The antipsychotic action of novel orthosteric and allosteric positive modulators of GABA-B receptor in mice. Br J Pharmacol 2010; In press
17. Dupuis DS, Relkovic D, Lhuillier L, et al. Point mutations in the transmembrane region of GABA-B2 facilitate activation by the positive modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) in the absence of the GABA-B1 subunit. Mol Pharmacol 2006;70:2027-2036
18. Orru A, Lai A, Lobina C, et al. Reducing effect of the positive allosteric modulators of the GABA-B receptor, CGP7930 and GS39783, on alcohol intake in alcohol-preferring rats. Eur J Pharmacol 2005;525:105-111
19. Liang JH, Chen F, Krstew E, et al. The GABA-B receptor allosteric modulator CGP7930, like baclofen, reduces operant self-administration of ethanol in alcohol-preferring rats. Neuropharmacology 2006;50:632-639
20. Filip M, Frankowska M, Przegalinski E. Effects of GABA-B receptor antagonist, agonists and allosteric positive modulator on the cocaine-induced self-administration and drug discrimination. Eur J Pharmacol 2007;574:148-157
21. Frankowska M, Golda A, Wydra K, et al. Effects of imipramine or GABA-B receptor ligands on the immobility, swimming and climbing in the forced swim test in rats following discontinuation of cocaine self-administration. Eur J Pharmacol 2010;627:142-149
22. Maccioni P, Pes D, Orru A, et al. Reducing effect of the positive allosteric modulator of the GABA-B receptor, GS39783, on alcohol self-administration in alcohol-preferring rats. Psychopharmacology 2007;193:171-178
23. Maccioni P, Fantini N, Froestl W, et al. Specific reduction of alcohol's motivational properties by the positive allosteric modulator of the GABA-Breceptor, GS39783: comparison with the effect of the GABA-B receptor direct agonist, baclofen. Alcohol Clin Exp Res 2008;32:1558-1564
24. Smith MA, Yancey DL, Morgan D, et al. Effects of positive allosteric modulators of the GABA-B receptor on cocaine self-administration in rats. Psychopharmacology 2004;173:105-111
25. Slattery DA, Markou A, Froestl W, Cryan JF. The GABA-B receptor-positive modulator GS39783 and the GABA-B receptor agonist baclofen attenuate the reward-facilitating effects of cocaine: intercranial self-stimulation studies in the rat. Neuropsychopharmacology 2005;30:2065-2072
26. Lhuillier L, Mombereau C, Cryan CF, et al. GABA-B receptor-positive modulation decreases selective molecular and behavioral effects of cocaine. Neuropsychopharmacology 2007;32:388-398
27. Mombereau C, Lhuillier L, Kaupmann K, et al. GABA-B receptor-positive modulation-induced blockade of the rewarding properties of nicotine is associated with a reduction in nucleus accumbens DeltaFosB accumulation. J Pharmacol Exp Ther 2007;321:172-177
28. Paterson NE, Vlachou S, Guery S, et al. Positive modulation of GABA-B receptors decreased nicotine self-administration and counteracted nicotine-induced enhancement of brain reward function in rats. J Pharmacol Exp Ther 2008;326:306-314
29. Novartis AG; Pfannkuche H-J. Use of GABA-B receptor positive modulators in gastro-intestinal disorders. WO090731; 2003
30. Novartis AG; Floersheim P, Froestl W, Guery S, Kaupmann K, Koller M. Pyrimidine derivatives for the treatment of GABA-B mediated nervous system disorders. WO136442; 2006
31. Guery S, Floersheim P, Kaupmann K, Froestl W. Syntheses and optimization of new GS39783 analogues as positive allosteric modulators of GABA-B receptors. Bioorg Med Chem Lett 2007;17:6206-6211
32. Maccioni P, Carai MAM, Kaupmann K, et al. Reduction of alcohol's reinforcing and motivational properties by the positive allosteric modulator of the GABA-B receptor, BHF177, in alcohol-preferring rats. Alcohol Clin Exp Res 2009;33:1749-1756
33. Jacobson LH, Guery S, Froestl W, Gentsch C, et al. In vitro and in vivo characterization of a novel GABA-B receptor positive allosteric modulator [Abstract 824.5]. 38th Society for Neuroscience Annual Meeting; 19 November 2008
34. Addex Pharma S.A.; Riguet E, Campo B, Gibelin A, Mhalla K. Novel triazinedione derivatives as GABA-B receptor modulators. WO056257; 2008
35. F. Hoffmann-La Roche AG; Malherbe P, Masciadri R, Prinssen E, Spooren W, Thomas AW. 4-(Sulfanyl-pyrimidine-4-yl-methyl)-morpholine derivatives and related compounds as GABA receptor ligands for the treatment of anxiety, depression and epilepsy. WO094828; 2005
36. F. Hoffmann-La Roche AG; Malherbe P, Masciadri R, Norcross RD, Ratni H, Thomas AW. Quinoline as allosteric enhancers of the GABA-B receptors. WO048146; 2006
37. F. Hoffmann-La Roche AG; Malherbe P, Masciadri R, Norcross RD, Prinssen E. 3-Methanesulfonylquinolines as GABA-B enhancers. WO128802; 2006
38. F. Hoffmann-La Roche AG; Malherbe P, Masciadri R, Norcross RD, Ratni H, Thomas AW. Thieno-pyridine derivatives as GABA-B allosteric enhancers. WO063732; 2006
39. F. Hoffmann-La Roche AG; Malherbe P, Masciadri R, Norcross RD, Prinssen E. Hydroxy-propionic acid derivatives and hydroxy-benzofuran-2-one derivatives with affinity for the GABA-B receptor. WO014843; 2007
40. Malherbe P, Masciadri R, Norcross RD, et al. Characterization of (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one as a positive allosteric modulator of GABA-B receptors. Br J Pharmacol 2008;154:797-811
41. Alker AM, Grillet F, Malherbe P, et al. Efficient one-pot synthesis of the GABA-B positive allosteric modulator (R,S)-5,7-di-tert-butyl-3-hydroxy-3- trifluoromethyl-3 H-benzofuran-2-one. Synth Commun 2008;38:3398-3405
42. Advani T, Hensler J, Cheng K, et al. Stimulation of [35S]GTPgammaS binding by the GABA-B receptor agonists and positive modulators in different brain regions. Available from: http://www.fasebj.org/cgi/content/meeting- abstract/24/1-MeetingAbstracts/769.15
43. AstraZeneca AB; Bauer U, Brailsford W, Chhajlani V, Egner B, Fjellstrom O, Gustafsson L, Mattson J, Nilsson K, Olsson T. Imidazole variants as modulators of GABA receptor for the treatment of GI disorders. WO001750; 2006
44. AstraZeneca AB; Bauer U, Brailsford W, Gustafsson L, Saxin M, Svensson T. Imidazole derivatives for the treatment of gastrointestinal disorders. WO073298; 2007
45. AstraZeneca AB; Bauer U, Gustafsson L, Saxin M. Imidazoles as GABA-B receptor modulators. WO073299; 2007
46. AstraZeneca AB; Bauer U, Brailsford W, Gustafsson L, Svensson T. GABA-B receptor modulators. WO073300; 2007
47. AstraZeneca AB; Bauer U, Brailsford W, Cheng L, Jonforsen M, Raubacher F, Schell P, Svensson T. Imidazole derivatives as modulators of the GABA receptor for the treatment of gastrointestinal disorders. WO130313; 2008
48. AstraZeneca AB; Bauer U, Gustafsson L, Saxin M, Svensson T. Heterocyclic GABA-B modulators. WO073296; 2007
49. AstraZeneca AB; Bauer U, inventor. Pyrazoles for the treatment of GERD and IBS. WO073297; 2007
50. AstraZeneca AB; Cheng L, Karle M. Quinoline compounds having an activity against the GABA-B receptor. WO041904; 2009
51. AstraZeneca AB; Cheng L, Holmquist S, Raubacher F, Schell P. Xanthine compounds having a positive allosteric GABA-B receptor modulator effect. WO130314; 2008
52. AstraZeneca AB; Cheng L, Jonforsen M, Schell P. Pteridine compounds having activity on the GABA-B receptors. WO041905; 2009
53. Johann Wolfgang Goethe-Universitat Frankfurt am Main; Duthey B, Pfeffer J, Boehncke W-H. Use of GABA-B selective agonists for treating inflammatory skin diseases. WO083992; 2008
54. Gjoni T, Urwyler S. Receptor activation involving positive allosteric modulation, unlike full agonism, does not result in GABA-B receptor desensitization. Neuropharmacology 2008;55:1293-1299
55. Gjoni T, Urwyler S. Changes in the properties of allosteric and orthosteric GABA-B receptor ligands after a continuous, desensitizing agonist pretreatment. Eur J Pharmacol 2009;603:37-41
56. Gjoni T, Desrayaud S, Imobersteg S, Urwyler S. The positive allosteric modulator GS39783 enhances GABA-B receptor-mediated inhibition of cyclic AMP formation in rat striatum in vivo. J Neurochem 2006;96:1416-1422
57. Alstermark C, Amin K, Dinn SR, et al. Synthesis and pharmacological evaluation of novel gamma-aminobutyric acid type B (GABA-B) receptor agonists as gastroesophageal reflux inhibitors. J Med Chem 2008;51:4315-4320
58. Lehmann A, Antonsson M, Holmberg AA, et al. (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABA-B receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action. J Pharmacol Exp Ther 2009;331:504-512
59. Bredenoord AJ. Lesogaberan, a GABA-B agonist for the potential treatment of gastro-esophageal reflux disease. I Drugs 2009;12:576-584
60. Sternbach LH. The benzodiazepine story. J Med Chem 1979;22:1-7