Efficient generation, storage, and manipulation of fully flexible pharmacophore multiplets and their use in 3-D similarity searching

Journal of Chemical Information and Computer Sciences

Volumn 43, Issue 2, 2003, Pages 458-468

  Abrahamian, Edmond ^a   Fox, Peter C ^a   Nærum, Lars ^b,c   Thøger Christensen, Inge ^b   Thøgersen, Henning ^b   Clark, Robert D ^a  

^a TRIPOS INC   (United States)

^b NOVO NORDISK A S   (Denmark)

^c Arpida Ltd   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CONFORMATIONS; DATA COMPRESSION; DATABASE SYSTEMS; ENCODING (SYMBOLS); ONLINE SEARCHING; XML;

BITMAPS;

MOLECULAR STRUCTURE;

ANTIARRHYTHMIC AGENT; BENZAMIDE DERIVATIVE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; ESTROGEN RECEPTOR; PHENOTHIAZINE DERIVATIVE;

ARTICLE; CHEMISTRY; COMPUTER PROGRAM; CONFORMATION; DRUG ANTAGONISM; INFORMATION RETRIEVAL; METHODOLOGY; PHARMACOLOGY; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STATISTICS;

ADRENERGIC BETA-ANTAGONISTS; ANTI-ARRHYTHMIA AGENTS; BENZAMIDES; INFORMATION STORAGE AND RETRIEVAL; MOLECULAR CONFORMATION; PHARMACOLOGY; PHENOTHIAZINES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; RECEPTORS, ESTROGEN; SOFTWARE; STOCHASTIC PROCESSES;

EID: 0037363560     PISSN: 00952338     EISSN: None     Source Type: Journal    
DOI: 10.1021/ci025595r     Document Type: Conference Paper

References (36)

1. Brown, R. D.; Martin, Y. C. Use of Structure-Activity Data to Compare Structure-Based Clustering Methods and Descriptors for Use in Compound Selection. J. Chem. Inf. Comput. Sci. 1996. 36, 572-584.
2. Patterson, D. E.; Cramer, R. D.; Ferguson, A. M.; Clark, R. D.; Weinberger, L. E. Neighborhood Behavior: A Useful Concept for Validation of "Molecular Diversity" Descriptors. J. Med. Chem. 1996, 39, 3049-3059.
3. Ferguson, A. M.; Patterson, D. E.; Garr, C. D.; Underiner, T. L. Designing Chemical Libraries for lead Discovery. J. Biomolec. Screen. 1996, 1, 65-73.
4. Good, A. C.; Kuntz, I. D. Investigating the extension of pairwise distance pharmacophore measures to triplet-based descriptors. J. Comput.-Aided Mol. Design 1995, 9, 373-379.
5. Mason, J. S.; Morize, I.; Menard, P. R.; Cheney, D. L.; Hulme, C.; Labaudiniere, R. F. New 4-Point Pharmacophore Method for Molecular Similarity and Diversity Applications: Overview of the Method and Applications, Including a Novel Approach to the Design of Combinatorial Libraries Containing Privileged Substructures. J. Med. Chem. 1999, 42, 3251-3264.
6. McGregor, M. J.; Muskal, S. M. Pharmacophore Fingerprinting. 1. Application to QSAR and Focused Library Design. J. Chem. Inf. Comput. Sci. 1999, 39, 569-574.
7. McGregor, M. J.; Muskal, S. M. Pharmacophore Fingerprinting. 2. Application to Primary Library Design. J. Chem. Inf. Comput. Sci. 2000, 40, 117-125.
8. Matter, H.; Pötter, T. Comparing 3D Pharmacophore Triplets and 2D Fingerprints for Selecting Diverse Compound Subsets. J. Chem. Inf. Comput. Sci. 1999, 39, 1211-1225.
9. Mason, J. S.; Beno, B. R. Library design using BCUT chemistry-space descriptors and multiple four-point pharmacophore finger-prints: Simultaneous optimization and structure-based diversity. J. Mol. Graphics Mod. 2000, 18, 438-451.
10. Eksterowicz, J. E.; Evensen, E.; Lemmen, C.; Brady, G. P.; Lanctot, J. K.; Bradley, E. K.; Saiah, E.; Robinson, L. A.; Grootenhuis, P. D. J.; Blaney, J. M. Coupling structure-based design with combinatorial chemistry: application of active site derived pharmacophores with informative library design. J. Mol. Graph. Model. 2002, 20, 469-477.
11. Chen, X.; Rusinko, A., III; Young, S. S. Recursive Partitioning Analysis of a Large Structure-Activity Data Set Using Three-Dimensional Descriptors. J. Chem. Inf. Comput. Sci. 1998, 38, 1054-1062.
12. Good, A. C.: Mason, J. S.; Green, D. V. S.; Leach, A. R. Pharmacophore-Based Approaches to Combinatorial Library Design. In Combinatorial Library Design and Evaluation; Ghose, A. K., Viswanadhan, V. N., Eds.; Marcel Dekker: New York, NY. 2001; pp 399-428.
13. Cato, S. J. Exploring Phrarmacophores with Chem-X. In Pharmacophore Perception, Development, and Use in Drug Design; Güner, O., Ed.: International University Line; La Jolla, CA, 2000; pp 107-125.
14. SYBYL, SYBYL Selector, and UNITY are distributed by Tripos, Inc., 1699 S. Hanley Rd., St. Louis, MO 63144.
15. Good, A. C.; Lewis, R. A. New Methodology for Profiling Combinatorial Libraries and Screening Sets: Cleaning Up the Design Process with HARPick. J. Med. Chem. 1997, 40, 3926-3936.
16. Pickett, S. D.; Luttmann, C.; Guerin, V.; Laoui, A.; James, E. DIVSEL and COMPLIB - Strategies for the Design and Comparison of Combinatorial Libraries using Pharmacophoric Descriptors. J. Chem. Inf. Comput. Sci. 1998, 38, 144-150.
17. Pickett, S. D.; McLay, I. M.; Clark, D. E. Enhancing the Hit-to-Lead Properties of Lead Optimization Libraries. J. Chem. Inf. Comput. Sci. 2000, 40, 263-272.
18. CONCORD was developed by R. S. Pearlman, A. Rusinko, J. M. Skell, and R. Baducci at the University of Texas, Austin, and is distributed exclusively by Tripos, Inc., 1699 S. Hanley Rd., St. Louis, MO 63144.
19. CONFORT was developed by R. S. Pearlman and R. Balducci at the University of Texas, Austin, and is distributed by Tripos, Inc., 1699 S. Hanley Rd., St. Louis, MO 63144.
20. Hurst, T. Flexible 3D Searching: The Directed Tweak Technique. J. Chem. Inf. Comput. Sci. 1994, 34, 190-196.
21. Ash, S.; Cline, M. A.; Homer, R. W.; Hurst, T.; Smith, G. B. SYBYL Line Notation (SLN): A Versatile Language for Chemical Structure Representation. J. Chem. Inf. Comput. Sci. 1997, 37, 71-79.
22. Addition of a special "null" feature to the augmentation list acts as a sort of "wild card" and overrides such exclusion.
23. The Dictionary of Pharmacological Agents is compiled by Chapman and Hall/CRC, London. The searchable version used here was prepared and distributed by Tripos.
24. Barnum, D.; Greene, J.; Smellie, A.; Sprague, P. Identification of Common Functional Configurations Among Molecules. J. Chem. Inf. Comput. Sci. 1996, 36, 563-571.
25. Willett, P.; Winterman, V. A Comparison of Some Measures of Intermolecular Structural Similarity. Quant. Struct.-Act. Relat. 1986, 5, 18-25.
26. Willett, P.; Barnard, J. M.; Downs, G. M. Chemical Similarity Searching. J. Chem. Inf. Comput. Sci. 1998, 38, 983-996.
27. National Cancer Institute, Bethesda MD.; http://dtp.nci.nih.gov/.
28. The number of distance bins used was reduced to 12 in this case specifically so that 32-bit versions could be generated.
29. Mannhold, R.; Rekker, R. F.; Sonntag, C.; ter Laak, A. M.; Dross, K.; Polymerpoulos. Comparative Evaluation of the Predictive Power of Calculation Procedures for Molecular Lipophilicity. J, Pharm. Sci. 1995, 84, 1410-1419.
30. Nasrum, L.; Nørskov-Lauritsen, L.; Olesen, P. H. Scaffold Hopping and Optimization towards Libraries of Glycogen Kinase-3 Inhibitors. Bioorg. Med. Chem. Lett. 2002, 12, 1525-1528.
31. Waszkowycz, B.: Perkins, T. D. J.; Sykes, R. A.; Li. J. Large-scale virtual screening for discovering leads in the postgenomic era. IBM Systems J. 2001, 40, 360-376.
32. Waszkowycz, B.; Perkins, T.; Baxter, C.; Sykes, R.; Li, J.; Harrison, M. Receptor-Based Virtual Screening of Very Large Chemical Datasets. In Rational Approaches to Drug Design; Höltje, H.-D., Sippl, W., Eds.; Prous Science: Barcelona, 2001; pp 372-381.
33. Jørgensen, A. S.; Jacobsen, P.; Christiansen, L. B.; Bury, P. S.; Kanstrup, A.; Thorpe, S. M.; Bain, S.; Nærum, L.; Wassermann, K. Synthesis and Pharmacology of a Novel Pyrrolo[2,1,5-cd]indolizine (NNC 45-0095), a High Affinity Non-Steroidal Agonist for the Estrogen Receptor. Bioorg. Med. Chem. Lett. 2000, 10, 399-402.
34. Jørgensen, A. S.; Jacobsen, P.; Christiansen, L. B.; Bury, P. S.; Kanstrup, A.; Thorpe, S. M.; Bain, S.; Nærum, L.; Wassermann, K. Synthesis and Estrogen Receptor Affinities of Novel Pyrrolo[2,1,5-cd]indolizine Derivatives. Bioorg. Med. Chem. Lett. 2000, 10, 2383-2386.
35. Bury, P. S.; Christiansen, L. B.; Jacobsen, P.; Jørgensen, A. S.; Kanstrup. A.; Nærum, L.; Bain, S.; Fledelius, C.; Gissel, B.; Hansen, B. S.; Korsgaard, N.; Thorpe, S. M.; Wassermann, K. Synthesis and Pharmacological Evaluation of Novel cis-3,4-diaryl-hydroxychromanes as High-Affinity Partial Agonists for the Estrogen Receptor. Bioorg. Med. Chem. 2001, 10, 125-145.
36. Christiansen, L. B.; Wenckens, P. S.; Bury, P. S.: Gissel, B.; Hansen, B. S.; Thorpe, S. M.; Jacobsen, P.; Kanstrup, A.; Jørgensen, A. S.; Nærum, L.; Wassermann, K. Synthesis and Biological Evaluation of Novel Thio-Substituted Chromanes as High-Affinity Partial Agonists for the Estrogen Receptor. Bioorg. Med. Chem. Lett. 2002, 12, 17-19.