Principal components describing biological activities and molecular diversity of heterocyclic aromatic ring fragments

Journal of Medicinal Chemistry

Volumn 39, Issue 20, 1996, Pages 4065-4072

  Gibson, Samuel ^a   McGuire, Ross ^a   Rees, David C ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC COMPOUND; HETEROCYCLIC COMPOUND; RNA DIRECTED DNA POLYMERASE INHIBITOR; VIRUS ENZYME;

ARTICLE; DIPOLE; DRUG RECEPTOR BINDING; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS 1; LIPOPHILICITY; MOLECULAR RECOGNITION; MOLECULAR SIZE; STATISTICAL ANALYSIS; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION; SURFACE CHARGE;

CHEMISTRY, PHYSICAL; HETEROCYCLIC COMPOUNDS; HIV-1 REVERSE TRANSCRIPTASE; MOLECULAR STRUCTURE; POLYCYCLIC HYDROCARBONS, AROMATIC; REVERSE TRANSCRIPTASE INHIBITORS; SOFTWARE; STATISTICS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0029848429     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960058h     Document Type: Article

References (36)

1. Franke, R.; Gruska, A. Chapter 4. Multivariate Data Analysis of Chemical and Biological Data. In Methods and Principles in Medicinal Chemistry Vol. 2 Chemometric Methods in Molecular Design; Mannhold, R., Krogsgaard-Larsen, P., Timmerman, H., Eds.; VCH: Weinheim, 1993; pp 113-163.
2. Jonsson, J.; Eriksson, L.; Hellberg, S.; Sjöström, M.; Wold, S. Multivariate Parameterization of 55 Coded and Non-Coded Amino Acids. Quant. Struct.-Act. Relat. 1989, 8, 204-209.
3. Skagerberg, B.; Bonelli, D.; Clementi, S.; Cruciani, G.; Ebert, C. Principal Properties for Aromatic Substituents. A Multivariate Approach for Design in QSAR. Quant. Struct.-Act. Relat. 1989, 8, 32-38.
4. Stjernlöf, P.; Ennis, M. D.; Hansson, L. O.; Hoffman, R. L.; Ghazal, N. B.; Sundell, S.; Smith, M. W.; Svensson, K.; Carlsson, A.; Wikstrom, H. Structure-Activity Relationships in the 8-Amino 6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. 1. Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes. J. Med. Chem. 1995, 38, 2202-2216.
5. Domine, D.; Devillers, J.; Chastrette, M. A Nonlinear Map of Substituent Constants for selecting Test Series and Deriving Structure-Activity Relationships. 1. Aromatic Series. J. Med. Chem. 1994, 37, 973-980.
6. Domine, D.; Devillers, J.; Chastrette, M. A Nonlinear Map of Substituent Constants for selecting Test Series and Deriving Structure-Activity Relationships. 2. Aliphatic Series. J. Med. Chem. 1994, 37, 981-987.
7. Hansch, C.; Unger, S. H.; Forsythe, A. B. Strategy in Drug Design. Cluster Analysis as an Aid in the Selection of Substituents. J. Med. Chem. 1973, 16, 1217-1222.
8. Caruso, L.; Musumarra, G.; Katritzky, A. R. "Classical" and "Magnetic" Aromaticities as new Descriptors for Heteroaromatics in QSAR. Part 3 [1]. Principal Properties for Heteroaromatics. Quant. Struct.-Act. Relat. 1993, 12, 146-151.
9. Langer, T. Molecular Similarity Determination of Heteroaromatics using GRID, CoMFA and Multivariate Data Analysis. Quant. Struct.-Act. Relat. 1994, 13, 402-405.
10. Langer, T. Molecular Similarity Determination of Heteroarmoatics Using GRID, CoMFA and Multivariate Data Analysis. In QSAR and Molecular Modelling: Concepts, Computational Tools and Biological Applications; Sanz, F., Giraldo, J., Manaut, F., Eds.; J. R. Prous Science Publishers: Barcelona, 1995; pp 388-391.
11. Clementi, S.; Cruciani, G.; Fifi, P.; Valigi, R.; Musumarra, G. A new set of Principal Properties for Heteroaromatics Obtained by GRID. Quant. Struct.-Act. Relat. 1996, 15, 108-120.
12. Goodford, P. J. A Computational Procedure fro Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules. J. Med. Chem. 1985, 28, 849-857.
13. Katritzky, A. R.; Rees, C. W. In Comprehensive Heterocyclic Chemistry, Volume 8, Subject, Author, Ring and Data Indexes; Drayton, C. J., Ed.; Pergamon Press: Oxford, 1984; pp 927-1111.
14. Elguero, J.; Marzin, C.; Katritzky, A. R.; Linda, P. The Tautomerism of Heterocycles, Suppl. 1. In Advances in Heterocyclic Chemistry; Katritzky, A. R., Boulton, A. J., Eds.; Academic Press: New York, 1976; Chapter 4, pp 291-292.
15. The physicochemical descriptors used in this study are the same or closely related to those used in many previous QSAR investigations. For a review/discussion on these properties, see: Kubinyi, H. Chapter 3. Parameters. In Methods and Principles in Medicinal Chemistry Vol. 1, QSAR: Hansch Analysis and Related Approaches; Mannhold, R., Krogsgaard-Larsen, P., Timmerman, H., Eds.; VCH: Weinheim, 1993; pp 21-36.
16. The Chem-X suite of programs, developed and distributed by CDL, Chipping Norton, England.
17. Stewart, J. J. P. QCPE 455. QCPE Bull. 1889, 9 (1), 10.
18. Philips, A. C. QCPE 274. QCPE 1975, 11, 274.
19. Dearden, J. C.; Ghafourian, T. A Hydrogen Bond Parameter from Molecular Orbital Theory: Comparison with α-Values. J. Pharm. Pharmacol. 1993, 45 (Suppl. 2), 1143.
20. Debnath, A. K.; Lopez de Compadre, R. L.; Debnath, G.; Shusterman, A. J.; Hansch, C. Structure-Activity Relationship of Mutagenic Aromatic and Heteroaromatic Nitro Compounds. Correlation with Molecular Orbital Energies and Hydrophobicity. J. Med. Chem. 1991, 34, 786-797.
21. Lukovits, I. Quantitative Structure-Activity Relationships Employing Independant Quantum Chemical Indices. J. Med. Chem. 1983, 26, 1104-1109.
22. Selwood, D. L.; Livingstone, D. J.; Comley, J. C. W.; O'Dowd, A. B.; Hudson, A. T.; Jackson, P.; Jandu, K. J.; Rose, V. S.; Stables, J. N. Structure-Activity Relationships of Antifilarial Antimycin Analogues: A Multivariate Pattern Recognition Study. J. Med. Chem. 1990, 33, 136-142.
23. Verloop, A.; Hoogenstraaten, W.; Tipker, J. Development and Application of New Steric Substituent Parameters in Drug Design. In Medicinal Chemistry, 11 (VII, Drug Design); Ariëns, E. J., Ed.; Academic Press: New York, 1976; pp 165-207.
24. Verloop, A. The STERIMOL Approach to Drug Design; Marcel Dekker: New York, 1987.
25. CLOGP3, PCmodels version 4.34, Daylight Chemical Information Systems Inc., Irvine, CA.
26. Hansch, C.; Leo, A. Substituents Constants For Correlation Analysis in Chemistry and Biology; John Wiley & Sons, Inc.: New York, 1979.
27. Swain, C. G.; Lupton, E. C. Field and Resonance Components of Substituent Effects. J. Am. Chem. Soc. 1968, 90, 4328-4337.
28. Chatfield, C.; Collins, A. J. Introduction to Multivariate Analysis; Chapman and Hall: London, New York, 1980; pp 57-58.
29. Saari, W. S.; Wai, J. S.; Fisher, T. E.; Thomas, C. M.; Hoffman, J. M.; Rooney, C. S.; Smith, A. M.; Jones, J. H.; Bamberger, D. L.; Goldman, M. E.; O'Brien, J. A.; Nunberg, J. H.; Quintero, J. C.; Schleif, W. A.; Emini, E. A.; Anderson, P. S. Synthesis and evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase inhibitors. J. Med. Chem. 1992, 35, 3792-3802.
30. McFarland, J. W.; Gans, D. J. On the Significance of Clusters in the Graphical Display of Structure-Activity Data. J. Med. Chem. 1986, 29, 505-514.
31. Austel, V. A Manual Method for Systematic Drug Design. Eur. J. Med. Chem.-Chim. Ther. 1982, 17, 9-16.
32. Del Re, G.; Gavuzzo, E.; Giglio, E.; Lelj, F.; Mazza, F.; Zappia, V. Conformational Study of a Methylating Agent: The Crystal Structures of S-Methyl-L-methionine Chloride.HCl (Vitamin U Hydrochloride). Acta. Crystallogr. Sect. B. 1977, B33, 3289-3296.
33. Suzuki, T. J. QCPE 608. QCPE Bull. 1991, 11 (4), 73.
34. The SAS suite of statistical programs, SAS Institute Inc., Cary, NC.
35. McFarland, J. W.; Gans, D. J. Linear Discriminant Analysis and Cluster Significance Analysis. In Comprehensive Medicinal Chemistry, 1st ed.; Hansch, C., Sammes, P. G., Taylor, J. B., Eds.; Pergamon Press: Oxford, 1990; pp 675-689.
36. Microsoft Excel Version 5.0, Microsoft Corp.