Lead generation using pharmacophore mapping and three-dimensional database searching: Application to muscarinic M3 receptor antagonists

Journal of Medicinal Chemistry

Volumn 42, Issue 17, 1999, Pages 3210-3216

  Marriott, David P ^a   Dougall, Iain G ^a   Meghani, Premji ^a   Liu, Yu Jiang ^a   Flower, Darren R ^a,b  

^a Astra Charnwood ^*  (United Kingdom)

^b EDWARD JENNER INST FOR VACC RES   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BENZAMIDE DERIVATIVE; ESTER DERIVATIVE; KETONE DERIVATIVE; LEAD; MUSCARINIC M3 RECEPTOR ANTAGONIST;

ANIMAL TISSUE; ARTICLE; CHEMICAL STRUCTURE; CONTROLLED STUDY; DATA BASE; DRUG ACTIVITY; DRUG BINDING SITE; DRUG DESIGN; DRUG SELECTIVITY; DRUG STRUCTURE; GUINEA PIG; MALE; NONHUMAN; PHARMACOPHORE; RECEPTOR AFFINITY;

ANIMALS; CARBACHOL; GUINEA PIGS; MALE; MODELS, MOLECULAR; MUSCARINIC ANTAGONISTS; MUSCLE CONTRACTION; MUSCLE, SMOOTH; RECEPTOR, MUSCARINIC M3; RECEPTORS, MUSCARINIC; STRUCTURE-ACTIVITY RELATIONSHIP; TRACHEA;

EID: 0033606951     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980409n     Document Type: Article

References (38)

1. Goodford, P. J. A computational procedure for determining energetically favourable binding sites on biologically important macromolecules. J. Med. Chem. 1985, 28, 849-857.
2. Gillet, V. J.; Newell, W.; Mata, P.; Myatt, G.; Sike, S.; Zsoldos, Z.; Johnson, A. P. SPROUT: recent developments in the de novo design of molecules. J. Chem. Inf. Comput. Sci. 1994, 34, 207-217.
3. Willett, P. A review of 3-dimensional chemical-structure retrieval-systems. J. Chemom. 1992, 6, 289-305.
4. Brint, A. T.; Willett, P. Pharmacophoric pattern matching in files of 3D chemical structures: comparison of geometric searching algorithms. J. Mol. Graph. 1987, 5, 49-56.
5. Martin, Y. C. 3D Database searching in Drug Design. J. Med. Chem. 1992, 35, 2145-2154.
6. Manallack, D. T. Getting That Hit - 3d Database Searching In Drug Discovery. Drug Discov. Today 1996, 1, 231-238.
7. Buckley, M. J.; Bonner, T. I.; Buckley, C. M.; Braun, M. R. Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells. Mol. Pharmacol. 1989, 35, 469-476.
8. Caulfield, M. P. Muscarinic receptors - characterization, coupling and function. Pharmacol. Ther. 1993, 58, 319-379.
9. Wallis, R. M. Preclinical and clinical-pharmacology of selective muscarinic m(3) receptor antagonists. Life Sci. 1995, 56, 861-868.
10. Patent WO9306098-A1, W09204346-A.
11. Wu, E. S.; Griffith, R. C.; Loch, J. T.; Kover, A.; Murray, R. J.; Mullen, G. B.; Blosser, J. C.; Machulskis, A. C.; McCreedy, S. A. In vitro muscarinic activity of spiromuscarones and related analogues. J. Med. Chem. 1995, 38, 1558-1570.
12. Unpublished results.
13. Rusinko, A.; Sheridan, R. P.; Nilakantan, R.; Haraki, K. S.; Bauman, N.; Venkataraghavan, R. Using CONCORD to Construct a Large Database of Three-Dimensional Coordinates from Connection Tables. J. Chem. Inf. Comput. Sci. 1989, 29, 251-255.
14. Hendrickson, M. A.; Nicklaus, M. C.; Milne, G. W. A.; Zaharevitz, D. CONCORD and CAMBRIDGE: Comparison of Computer-Generated Chemical Structures with X-ray Crystallographic Data. J. Chem. Inf. Comput. Sci. 1993, 33, 155-163.
15. Flower, D. R. ALTER: Eclectic management of molecular structure data. J. Mol. Graph. Mod. 1997, 15, 161-169.
16. James, C. A.; Weininger, D. Daylight Theory Manual; Daylight Chemical Information Systems, Inc., 1995.
17. Bleasby, A. J.; Wootton, J. C. Construction of validated, nonredundant composite protein sequence databases. Protein Eng. 1990, 3, 153-159.
18. Gasteiger, J.; Rudolph, C.; Sadowski, J. Automatic generation of 3D-atomic coordinates for organic molecules. Tetrahedron Comput. Methods 1990, 3, 537-547.
19. UNITY 2.4; Tripos Inc., 1699 South Hanley Rd, St. Louis, MO, 63144.
20. SYBYL 6.2; Tripos Inc., 1699 South Hanley Rd, St. Louis, MO, 63144.
21. Allen, F. H.; Bellard, S.; Brice, M. D.; Cartwright, B. A.; Doubleday, A.; Higgs, H.; Hummelink, T.; Hummelink-Peters, B. G.; Kennard, O.; Motherwell, W. D. S.; Rodgers, J. R.; Watson, D. G. The Cambridge crystal data centre: computer-based search, retrieval, analysis, and display of information. Acta Crystallogr. 1979, B35, 2331-2339.
22. Martin, Y.; Bures, M.; Dahaner, E.; DeLazzer, J.; Lico, I.; Pavlik, P. A Fast Approach to Pharmacophore Mapping and its Application to Dopaminergic and Benzodiazepine Agonists. J. Comput. - Aided Mol. Des. 1993, 7, 83-102.
23. Leff, P.; Dougall, I. G.; Harper, D. Estimation of partial agonist affinity by interaction with a full agonist: a direct operational model-fitting approach. Br. J. Pharmacol. 1993, 110, 239-244.
24. Jenkinson, D. H.; Barnard, E. A.; Hoyer, D.; Humphrey, P. P. A.; Leff, P.; Shankley, N. P. International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. IX. Recommendations on Terms and Symbols in Quantitative Pharmacology. Pharmacol. Rev. 1995, 47, 255-266.
25. x and competitive drug antagonism. Br. J. Pharmacol. 1949, 4, 277-280.
26. Jakes, S. E.; Watts, N.; Willett, P.; Bawden, D.; Fisher, J. D. Pharmacophoric pattern matching in files of 3D chemical structures: evaluation of search performance. J. Mol. Graph. 1987, 5, 41-48.
27. Schmidt, A. W.; Peroutka, S. J. Three-dimensional steric molecular modeling of the 5-hydroxytryptamine3 receptor pharmacophore. Mol. Pharmacol. 1989, 36, 505-511.
28. Swain, C. J.; Baker, R.; Kneen, C.; Moseley, J.; Saunders, J.; Seward, E. M.; Stevenson, G.; Beer, M.; Stanton, J.; Watling, K. Novel 5-HT3 antagonists. Indole oxadiazoles. J. Med. Chem. 1991, 34, 140-151.
29. Hibert, M. F.; Hoffman, R.; Miller, R. C.; Carr, A. A. Conformation-Activity Relationship Study of 5-HT3 Receptor Antagonists and a definition of a Model for this Receptor Site. J. Med. Chem. 1990, 33, 1594-1600.
30. Buchheit, K. H.; Gamse, R.; Giger, R.; Hoyer, D.; Klein, F.; Kloppner, E.; Pfannkuche, H. J.; Mattes, H. The serotonin 5-HT4 receptor. 1. Design of a new class of agonists and receptor map of the agonist recognition site. J. Med. Chem. 1995, 38, 2326-2330.
31. Borea, P. A.; Bertolasi, V.; Gilli, G. Crystallographic and conformational studies on Histamine H1-receptor Antagonists. Arzneim.-Forsch. / Drug Res. 1986, 36, 895-899.
32. Mayer, D.; Naylor, C. B.; Motoc, I.; Marshall, G. R. A unique geometry of the active site of angiotensin-converting enzyme consistent with structure-activity studies. J. Comput.-Aided Mol. Des. 1987, 1, 3-16.
33. Melacini, G.; Zhu, Q.; Osapay, G.; Goodman, M. A refined model for the somatostatin pharmacophore: conformational analysis of lanthionine-sandostatin analogues. J. Med. Chem. 1997, 40, 2252-2258.
34. Nicklaus, M. C.; Neamati, N.; Hong, H.; Mazumder, A.; Sunder, S.; Chen, J.; Milne, G. W.; Pommier, Y. HIV-1 integrase pharmacophore: discovery of inhibitors through three-dimensional database searching. J. Med. Chem. 1997, 40, 920-929.
35. Hong, H.; Neamati, N.; Wang, S.; Nicklaus, M. C.; Mazumder, A.; Zhao, H.; Burke, T. R., Jr.; Pommier, Y.; Milne, G. W. Discovery of HIV-1 integrase inhibitors by pharmacophore searching. J. Med. Chem. 1997, 40, 930-936.
36. Wang, S.; Zaharevitz, D. W.; Sharma, R.; Marquez, V. E.; Lewin, N. E.; Du, L.; Blumberg, P. M.; Milne, G. W. The discovery of novel, structurally diverse protein kinase C agonists through computer 3D-database pharmacophore search. Molecular modeling studies. J. Med. Chem. 1994, 37, 4479-4489.
37. Lee, J.; Wang, S.; Milne, G. W.; Sharma, R.; Lewin, N. E.; Blumberg, P. M.; Marquez, V. E. Conformationally constrained analogues of diacylglycerol. 11. Ultrapotent protein kinase C ligands based on a chiral 5-disubstituted tetrahydro-2-furanone template. J. Med. Chem. 1996, 39, 29-35.
38. Wang, S.; Milne, G. W.; Nicklaus, M. C.; Marquez, V. E.; Lee, J.; Blumberg, P. M. Protein kinase C Modeling of the binding site and prediction of binding constants. J. Med. Chem. 1994, 37, 1326-1338.