Discovery of potent positive allosteric modulators of the α3β2 nicotinic acetylcholine receptor by a chemical space walk in chembl

ACS Chemical Neuroscience

Volumn 5, Issue 5, 2014, Pages 346-359

  Bürgi, Justus J ^a   Awale, Mahendra ^a   Boss, Silvan D ^a   Schaer, Tifany ^b   Marger, Fabrice ^b   Viveros Paredes, Juan M ^c   Bertrand, Sonia ^b   Gertsch, Jürg ^a   Bertrand, Daniel ^b   Reymond, Jean Louis ^a  

^a UNIVERSITY OF BERN   (Switzerland)

^b HiQScreen   (Switzerland)

^c UNIVERSITY OF GUADALAJARA   (Mexico)

Author keywords

[No Author keywords available]

Indexed keywords

(2,3 DIHYDRO 1H ISOINDOLE 2 YL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (1,3 BENZODIOXOL 5 YLMETHYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (2 BROMOBENZYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (2 CHLOROBENZYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (2 IODOBENZYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (2 METHYLBENZYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (2,4 DICHLOROBENZYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (2,6 DICHLOROBENZYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (4 CHLOROBENZYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (NAPHTHALENE 2 YLMETHYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (PYRIDIN 2 YLMETHYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N (PYRIDIN 4 YLMETHYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N BENZYL 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N [(R) 1 PHENYLETHYL] 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N [(S) 1 PHENYLETHYL] 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N(2 METHOXYBENZYL) 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; N,N DIBENZYL 1 AZABICYCLO[2.2.2]OCTAN 3 AMINE; NICOTINIC AGENT; NICOTINIC RECEPTOR; NICOTINIC RECEPTOR ALPHA3BETA2; UNCLASSIFIED DRUG; BENZAMIDE DERIVATIVE; BICYCLO COMPOUND; PNU-282987;

ALKYLATION; ALLOSTERISM; ANIMAL EXPERIMENT; ARTICLE; BODY TEMPERATURE; CARBON NUCLEAR MAGNETIC RESONANCE; COMPETITIVE INHIBITION; CONTROLLED STUDY; ELECTROPHYSIOLOGY; ELEVATED PLUS MAZE TEST; ENANTIOMER; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; ROTAROD TEST; VOLTAGE CLAMP TECHNIQUE; WALKING; ANIMAL; CHEMICAL DATABASE; CHEMICAL MODEL; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; GENETICS; HUMAN; MEMBRANE POTENTIAL; METABOLISM; XENOPUS LAEVIS;

ALLOSTERIC REGULATION; ANIMALS; BENZAMIDES; BICYCLO COMPOUNDS; DATABASES, CHEMICAL; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MEMBRANE POTENTIALS; MICE; MODELS, CHEMICAL; NICOTINIC AGONISTS; RECEPTORS, NICOTINIC; XENOPUS LAEVIS;

EID: 84901251721     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn4002297     Document Type: Article

References (38)

1. Wang, Y., Xiao, J., Suzek, T. O., Zhang, J., Wang, J., and Bryant, S. H. (2009) PubChem: a public information system for analyzing bioactivities of small molecules Nucleic Acids Res. 37, W623-W633
2. Gaulton, A., Bellis, L. J., Bento, A. P., Chambers, J., Davies, M., Hersey, A., Light, Y., McGlinchey, S., Michalovich, D., Al-Lazikani, B., and Overington, J. P. (2012) ChEMBL: a large-scale bioactivity database for drug discovery Nucleic Acids Res. 40, D1100-D1107
3. Ruddigkeit, L., Van Deursen, R., Blum, L. C., and Reymond, J. L. (2012) Enumeration of 166 billion organic small molecules in the chemical universe database GDB-17 J. Chem. Inf. Model. 52, 2864-2875
4. Bajorath, J. (2012) Modeling of activity landscapes for drug discovery Expert Opin. Drug Discovery 7, 463-473
5. D'Hoedt, D. and Bertrand, D. (2009) Nicotinic acetylcholine receptors: an overview on drug discovery Expert Opin. Ther. Targets 13, 395-411
6. Fagerlund, M. J. and Eriksson, L. I. (2009) Current concepts in neuromuscular transmission Br. J. Anaesth. 103, 108-114
7. Tsuneki, H., Kimura, I., Dezaki, K., Kimura, M., Sala, C., and Fumagalli, G. (1995) Immunohistochemical localization of neuronal nicotinic receptor subtypes at the pre- and postjunctional sites in mouse diaphragm muscle Neurosci. Lett. 196, 13-16
8. www.tocris.com.
9. Bodnar, A. L., Cortes-Burgos, L. A., Cook, K. K., Dinh, D. M., Groppi, V. E., Hajos, M., Higdon, N. R., Hoffmann, W. E., Hurst, R. S., Myers, J. K., Rogers, B. N., Wall, T. M., Wolfe, M. L., and Wong, E. (2005) Discovery and structure-activity relationship of quinuclidine benzamides as agonists of alpha7 nicotinic acetylcholine receptors J. Med. Chem. 48, 905-908
10. Lipinski, C. A., Lombardo, F., Dominy, B. W., and Feeney, P. J. (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings Adv. Drug Delivery Rev. 23, 3-25
11. Bohacek, R. S., McMartin, C., and Guida, W. C. (1996) The art and practice of structure-based drug design: a molecular modeling perspective Med. Res. Rev. 16, 3-50
12. Reymond, J. L., Van Deursen, R., Blum, L. C., and Ruddigkeit, L. (2010) Chemical space as a source for new drugs MedChemComm 1, 30-38
13. Renner, S., Popov, M., Schuffenhauer, A., Roth, H. J., Breitenstein, W., Marzinzik, A., Lewis, I., Krastel, P., Nigsch, F., Jenkins, J., and Jacoby, E. (2011) Recent trends and observations in the design of high-quality screening collections Future Med. Chem. 3, 751-766
14. Reymond, J. L. and Awale, M. (2012) Exploring Chemical Space for Drug Discovery Using the Chemical Universe Database ACS Chem. Neurosci. 3, 649-657
15. Pearlman, R. S. and Smith, K. M. (1998) Novel software tools for chemical diversity Persp. Drug Discovery Des. 9-11, 339-353
16. Oprea, T. I. and Gottfries, J. (2001) Chemography: The art of navigating in chemical space J. Comb. Chem. 3, 157-166
17. Nguyen, K. T., Blum, L. C., van Deursen, R., and Reymond, J.-L. (2009) Classification of Organic Molecules by Molecular Quantum Numbers ChemMedChem 4, 1803-1805
18. Reymond, J. L., Blum, L. C., and Van Deursen, R. (2011) Exploring the Chemical Space of Known and Unknown Organic Small Molecules Chimia 65, 863-867 www.gdb.unibe.ch
19. Ruddigkeit, L., Blum, L. C., and Reymond, J. L. (2013) Visualization and virtual screening of the chemical universe database GDB-17 J. Chem. Inf. Model. 53, 56-65
20. van Deursen, R., Blum, L. C., and Reymond, J. L. (2010) A searchable map of PubChem J. Chem. Inf. Model. 50, 1924-1934
21. Blum, L. C., van Deursen, R., and Reymond, J. L. (2011) Visualisation and subsets of the chemical universe database GDB-13 for virtual screening J. Comput.-Aided Mol. Des. 25, 637-647
22. van Deursen, R., Blum, L. C., and Reymond, J. L. (2011) Visualisation of the chemical space of fragments, lead-like and drug-like molecules in PubChem J. Comput.-Aided Mol. Des. 25, 649-662
23. Blum, L. C., van Deursen, R., Bertrand, S., Mayer, M., Burgi, J. J., Bertrand, D., and Reymond, J. L. (2011) Discovery of α7-Nicotinic Receptor Ligands by Virtual Screening of the Chemical Universe Database GDB-13 J. Chem. Inf. Model. 51, 3105-3112
24. Awale, M. and Reymond, J. L. (2012) Cluster analysis of the DrugBank chemical space using molecular quantum numbers Bioorg. Med. Chem. 20, 5372-5378
25. Bartos, M., Price, K. L., Lummis, S. C., and Bouzat, C. (2009) Glutamine 57 at the complementary binding site face is a key determinant of morantel selectivity for α7 nicotinic receptors J. Biol. Chem. 284, 21478-21487
26. Seo, S., Henry, J. T., Lewis, A. H., Wang, N., and Levandoski, M. M. (2009) The positive allosteric modulator morantel binds at noncanonical subunit interfaces of neuronal nicotinic acetylcholine receptors J. Neurosci. 29, 8734-8742
27. Wu, T. Y., Smith, C. M., Sine, S. M., and Levandoski, M. M. (2008) Morantel allosterically enhances channel gating of neuronal nicotinic acetylcholine alpha 3 beta 2 receptors Mol. Pharmacol. 74, 466-475
28. Cesa, L. C., Higgins, C. A., Sando, S. R., Kuo, D. W., and Levandoski, M. M. (2012) Specificity Determinants of Allosteric Modulation in the Neuronal Nicotinic Acetylcholine Receptor: A Fine Line between Inhibition and Potentiation Mol. Pharmacol. 81, 239-249
29. Garcia-Delgado, N., Bertrand, S., Nguyen, K. T., van Deursen, R., Bertrand, D., and Reymond, J.-L. (2010) Exploring α7-Nicotinic Receptor Ligand Diversity by Scaffold Enumeration from the Chemical Universe Database GDB ACS Med. Chem. Lett. 1, 422-426
30. Brethous, L., Garcia-Delgado, N., Schwartz, J., Bertrand, S., Bertrand, D., and Reymond, J. L. (2012) Synthesis and Nicotinic Receptor Activity of Chemical Space Analogues of N -(3 R)-1-Azabicyclo[2.2.2]oct-3-yl-4- chlorobenzamide (PNU-282,987) and 1,4-Diazabicyclo[3.2.2]nonane-4-carboxylic Acid 4-Bromophenyl Ester (SSR180711) J. Med. Chem. 55, 4605-4618
31. Hogg, R. C., Bandelier, F., Benoit, A., Dosch, R., and Bertrand, D. (2008) An automated system for intracellular and intranuclear injection J. Neurosci. Methods 169, 65-75
32. Vicens, P., Ribes, D., Heredia, L., Torrente, M., and Domingo, J. L. (2013) Motor and anxiety effects of PNU-282987, an α7 nicotinic receptor agonist, and stress in an animal model of Alzheimer's disease Curr. Alzheimer Res. 10, 516-523
33. Brioni, J. D., O'Neill, A. B., Kim, D. J., and Decker, M. W. (1993) Nicotinic receptor agonists exhibit anxiolytic-like effects on the elevated plus-maze test Eur. J. Pharmacol. 238, 1-8
34. Turner, J. R., Castellano, L. M., and Blendy, J. A. (2010) Nicotinic partial agonists varenicline and sazetidine-A have differential effects on affective behavior J. Pharmacol. Exp. Ther. 334, 665-672
35. Wallace, T. L., Callahan, P. M., Tehim, A., Bertrand, D., Tombaugh, G., Wang, S., Xie, W., Rowe, W. B., Ong, V., Graham, E., Terry, A. V., Rodefer, J. S., Herbert, B., Murray, M., Porter, R., Santarelli, L., and Lowe, D. A. (2011) RG3487, a Novel Nicotinic α7 Receptor Partial Agonist, Improves Cognition and Sensorimotor Gating in Rodents J. Pharmacol. Exp. Ther. 336, 242-253
36. Willett, P., Barnard, J. M., and Downs, G. M. (1998) Chemical Similarity Searching J. Chem. Inf. Comput. Sci. 38, 983-996
37. Gottlieb, H. E., Kotlyar, V., and Nudelman, A. (1997) NMR Chemical Shifts of Common Laboratory Solvents as Trace Impurities J. Org. Chem. 62, 7512-7515
38. Abdel-Magid, A. F., Carson, K. G., Harris, B. D., Maryanoff, C. A., and Shah, R. D. (1996) Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures(1) J. Org. Chem. 61, 3849-3862