The use of a pharmacophore model for identification of novel ligands for the benzodiazepine binding site of the GABA A receptor

Journal of Molecular Graphics and Modelling

Volumn 23, Issue 3, 2004, Pages 253-261

  Kahnberg, Pia ^a   Howard, Michael H ^b   Liljefors, Tommy ^c   Nielsen, Mogens ^c   Nielsen, Elsebet Østergaard ^d   Sterner, Olov ^a   Pettersson, Ingrid ^e  

^a LUND UNIVERSITY   (Sweden)

^b DUPONT COMPANY   (United States)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

^d NEUROSEARCH A S   (Denmark)

^e NOVO NORDISK A S   (Denmark)

Author keywords

Benzodiazepine site; Catalyst; Conformational analysis; Database searching; Flavones; GABA A; Hydrogen bonding; Pharmacophore

Indexed keywords

FLAVONOIDS; LIGANDS; PHARMACOPHORE MODEL;

CONFORMATIONS; OPTIMIZATION;

CATALYSTS;

4 AMINOBUTYRIC ACID A RECEPTOR; BENZODIAZEPINE RECEPTOR; FLAVONOID;

ARTICLE; DRUG BINDING SITE; DRUG RECEPTOR BINDING; MOLECULAR MODEL; PHARMACOPHORE; PRIORITY JOURNAL; RECEPTOR AFFINITY; VALIDATION PROCESS;

ANIMALS; BENZODIAZEPINES; BINDING SITES; COMPUTER SIMULATION; DATABASES, FACTUAL; DRUG DESIGN; FLAVONOIDS; GABA MODULATORS; HUMANS; HYDROGEN BONDING; LIGANDS; MODELS, CHEMICAL; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; RECEPTORS, GABA-A;

EID: 7744242103     PISSN: 10933263     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmgm.2004.06.003     Document Type: Article

References (41)

1. A receptor research Synapse 21 1995 189 274
2. A receptor channels Annu. Rev. Neurosci. 17 1994 569 602
3. C receptors: relatively simple transmitter-gated ion channels TiPS 17 1996 319 323
4. B receptors uncovers similarity to metabotropic glutamate receptors Nature 386 1997 239 246
5. A receptor subtypes 38th ed. 1995 Academic Press New York
6. A receptor subtypes Pharmacol. Rev. 47 1995 181 234
7. C.R. Gardner, W.R. Tully, and J.R. Hedgecock The rapidly expanding range of neuronal benzodiazepine ligands Prog. Neurobiol. 40 1993 1 61
8. J.H.M. Medina, H. Violoa, C. Wolfman, M. Marder, C. Wasowskj, D. Calvo, and A.C. Paladini Neuroactive flavonoids; new ligands for the benzodiazepine receptors Phytomedicine. 5 1998 235 243
9. A/benzodiazepine receptor as a target for psychoactive drugs 1996 Springer-Verlag Heidelberg, Germany
10. W. Zhang, K.F. Koehler, P. Zhang, and J.M. Cook Development of a comprehensive pharmacophore model for the benzodiazepine receptor Drug Des. Discovery 12 1995 193 248
11. A receptor complex J. Med. Chem. 42 1999 4343 4350
12. A receptor J. Med. Chem. 45 2002 4188 4201
13. J. Green, S. Kahn, H. Savoj, P. Sprague, and S. Teig Chemical function queries for 3D database search J. Chem. Inf. Comput. Sci. 34 1994 1297 1308
14. A. Smellie, S.D. Kahn, and S. Teig Analysis of conformational coverage. 1. Validation and estimation of coverage J. Chem. Inf. Comput. Sci. 35 1995 285 294
15. A. Smellie, S.D. Kahn, and S. Teig An analysis of conformational coverage 2. Applications of conformational models J. Chem. Inf. Comput. Sci. 35 1995 295 304
16. A. Smellie, S.L. Teig, and P. Towbin Poling: promoting conformational variation J. Comp. Chem. 16 1995 171 187
17. M. Hahn Three-dimensional shape-based searching of conformationally flexible compounds J. Chem. Inf. Comput. Sci. 37 1997 80 86
18. P.W. Sprague Automated Chemical Hypothesis Generation and Database Searching with Catalyst K. Miiller Perspectives in Drug Discovery and Design vol. 3 1995 ESCOM Science Publishers B. V 1 20
19. Y. Kurogi, and O.F. Güner Pharmacophore modeling and three-dimensional database searching for drug design using Catalyst Curr. Med. Chem. 8 2001 1035 1055
20. M. Grigorov, J. Weber, J.M.J. Tronchet, C.W. Jefford, W.K. Milhous, and D. Maric A QSAR study of the antimalarial activity of some synthetic 1,2,4-Trioxanes J. Chem. Inf. Comput. Sci. 37 1997 124 130
21. E.A. Hecker, C. Duraiswami, T.A. Andrea, and D.J. Diller Use of Catalyst pharmacophore models for screening of large combinatorial libraries J. Chem. Inf. Comput. Sci. 42 2002 1204 1211
22. G.C. Chen, C.-S. Chang, W.M. Kan, C.-L. Chang, K.C. Wang, and J.-W. Chern Novel lead generation through hypothetical pharmacophore three-dimensional database searching: discovery of isoflavanoids as nonsteriodal inhibitors of rat 5α-Reductase J. Med. Chem. 44 2001 3759 3763
23. Y. Koide, T. Hasegawa, A. Takahashi, A. Endo, N. Mochizuki, M. Nakagawa, and A. Nishida Development of novel EDG3 antagonists using a 3D database search and their structure-activity relationships J. Med. Chem. 45 2002 4629 4638
24. R. Griffith, R. Chanphen, S.P. Leach, and P.A. Keller New anti-malarial compounds from database searching Bioorg. Med. Chem. Lett. 12 2002 539 542
25. Y. Kurogi, K. Miyata, T. Okamura, K. Hashimoto, K. Tsutsumi, M. Nasu, and M. Moriyasu Discovery of novel mesangial cell proliferation inhibitors using a three-dimensional database searching method J. Med. Chem. 44 2001 2304 2307
26. Catalyst, version 4.6; Accelrys Inc., 9685 Scranton Road, San Diego, CA 92121, www.accelrys.com.
27. T.A. Halgren Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 J. Comput. Chem. 17 1996 490 519
28. T.A. Halgren Merck molecular force field. II. MMFF94 van der waals and electrostatic parameters for intermolecular interactions J. Comput. Chem. 17 1996 520 552
29. T.A. Halgren Merck molecular force field. III. Molecular geometries and vibrational frequencies for MMFF94 J. Comput. Chem. 17 1996 553 586
30. T.A. Halgren, and R.B. Nachbar Merck molecular force field. IV. Conformational energies and geometries for MMFF94 J. Comput. Chem. 17 1996 587 615
31. T.A. Halgren Merck molecular force field. V. Extension of MMFF94 using experimental data, additional computational data, and empirical rules J. Comput. Chem. 17 1996 616 641
32. T.A. Halgren MMFF VI. MMFF94s option for energy minimization studies J. Comput. Chem. 20 1999 720 729
33. T.A. Halgren MMFF VII. Characterization of MMFF94, MMFF94s, and other widely available force fields for conformational energies and for intermolecular-interaction energies and geometries J. Comput. Chem. 20 1999 730 748
34. G. Chang, W.C. Guida, and W.C. Still An internal coordinate Monte Carlo method for searching conformational space J. Am. Chem. Soc. 111 1989 4379 4386
35. Schrödinger Inc. www.schrodinger.com
36. F. Mohamadi, N.G.J. Richards, W.C. Guida, R. Liskamp, M. Lipton, C. Caufield, G. Chang, T. Hendrickson, and W.C. Still MacroModel - An integrated software system for modeling organic and bioorganic molecules using molecular mechanics J. Comp. Chem. 11 1990 440 467
37. W.C. Still, A. Tempczyk, R.C. Hawley, and T. Hendrickson Semianalytical treatment of solvation for molecular mechanics and dynamics J. Am. Chem. Soc. 112 1990 6127 6129
38. J. Boström, P.-O. Norrby, and T. Liljefors Conformational energy penalties of protein-bound ligands J. Computer-Aided Mol. Design. 12 1998 383 396
39. A.D. Settimo, G. Primofiore, F.D. Settimo, A.M. Marini, E. Novellino, G. Greco, C. Martini, G. Giannaccini, and A. Lucacchini Synthesis, structure-activity relationships, and molecular modeling studies of N-(Indol-3-ylglyoxylyl)benzylamine derivatives acting at the benzodiazepine receptor J. Med. Chem. 39 1996 5083 5091
40. A.D. Settimo, G. Primofiore, F.D. Settimo, A.M. Marini, E. Novellino, G. Greco, M. Gesi, C. Martini, G. Giannaccini, and A. Lucacchini N′-Phenylindol-3-ylglyoxylohydrazide derivatives: synthesis, structure-activity relationships, molecular modeling studies, and pharmacological action on brain benzodiazepine receptors J. Med. Chem. 41 1998 3821 3830
41. G. Primofiore, F.D. Settimo, S. Taliani, A.M. Marini, E. Novellino, G. Greco, A. Lavecchia, F. Besnard, L. Trincavelli, B. Costa, and C. Martini Novel N-(Arylalkyl)indol-3-ylglyoxylylamides targeted as ligands of the benzodiazepine receptor: synthesis, biological evaluation, and molecular modeling analysis of the structure-activity relationships J. Med. Chem. 44 2001 2286 2297