QSAR and CoMFA: A perspective on the practical application to drug discovery

Drug Design and Discovery

Volumn 17, Issue 1, 2000, Pages 4-12

  Podlogar, Brent L ^a   Ferguson, David M ^b  

^a BAYER CORPORATION   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LIGAND;

ANALYTICAL ERROR; DRUG CONFORMATION; DRUG DESIGN; METHODOLOGY; REVIEW;

DRUG DESIGN; MODELS, MOLECULAR; MOLECULAR CONFORMATION; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0034089732     PISSN: 10559612     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (35)

1. Lahana, R. How Many Leads from HTS? Drug Disc. Today, 1999, 4, 447-448.
2. Cramer III, R. D.; Patterson, D. E.; Bunce, J. D. Comparative Molecular Field Analysis (CoMFA). 1. Effect of Shape on Binding of Steroids to Carrier Proteins. J. Am. Chem. Soc. 1988, 110, 5959-5967.
3. Sufrin, J. R.; Dunn, D. A.; Marshall, G. R. Steric Mapping of the 1-Methionine Binding Site of ATP:L-Methiomne S-Adenosyltransferase. Mol. Pharm. 1981, 19, 307-317.
4. Chen, J. Z.; Hu, L. H.; Jiang, H. L.; Gu, J. D.; Zhu, W. L.; Chen, Z. L.; Chen, K. X.; Ji, R. Y. A 3D-QSAR Study on Ginkgolides and their Analogues with Comparative Molecular Field Analysis. Bioorg. Med. Chem. Lett. 1998, 8, 1291-1296.
5. 1 Receptors. A Comparison of CoMFA Models. J. Med. Chem., 1997, 40, 1648-1656.
6. Podlogar, B. L.; Paterlini, M. G.; Leo, G. C.; Ferguson, D. M.; Demeter, D. A.; Brown, F. K.; Reitz, A. B. "Conformational Analysis of the Endogenous μ-Opioid Agonist Endomorphin-1 Using NMR Spectroscopy and Molecular Modeling," FEBS Letters, 1998, 439, 13-20.
7. Matter, H.; Schwab, W.; Barbier, D.; Billen, G.; Hasse, B.; Neises, B.; Schudok, M.; Thorwart, W.; Schreuder, H.; Brachvogel, V.; Lonze, P.; Weithmann K.U. Quantitative Structure-Activity Relationship of Human Neutrophil Collagenase (MMP-8) Inhibitors Using Comparitive Molecular Field Analysis and X-ray Structure Analysis, J. Med. Chem., 1999, 42, 1908-1920.
8. Bernard, P.; Kireev, D. B.; Chretien, J.R.; Fortier, P. L.; Coppet, L. Automated Docking of 82 N-benzylpiperidine Derivatives to Mouse Acetylcholinesterase and Comparative Molecular Field Analysis with 'Natural' Alignment. J. Comput. Aided Mol. Des. 1999, 13, 355-371.
9. Shoichet, B. K.; Bodian, D. L.; Kuntz, I. D. Molecular Docking Using Shape Descriptors. J. Comp. Chem. 1992, 13, 380-397.
10. Subramanian, G.; Paterlini, M. G.; Larson, D. L.; Portoghese, P. S; Ferguson, D. M. Conformational Analysis and Automated Receptor Docking of Delective Arylacetamide-Based Kappa-Opioid Agonists. J. Med. Chem. 1998, 41, 4777-4789.
11. Subramanian, G.; Paterlini, M.G.; Portoghese, P. S.; Ferguson, D. M. Molecular Docking Reveals a Novel Binding Site Model for Fentanyl at the μ-Opioid Receptor. J. Med. Chem. 2000, 43, 381-91.
12. Podlogar, B. L.; Mugge, I.; Andreani R. QSAR Analysis of Biphenylcarbonyl MMP-3 Inhibitors Using Alternative Alignment Methods and Automated Docking. Manuscript in preparation.
13. Huang Q.; Cox, E. D.; Gan, T.; Ma, C.; Bennett, D. W.; McKernan, R. M.; Cook, J. M. Studies of Molecular Pharmacophore/Receptor Models for GABAA/Benzodiazapine Receptor Subtypes: Binding Affinities of Substituted b-Carbolines at Recombinant αxβ3γ2 Subtypes and Quantitative Structure-Activity Relationship Studies via a Comparative Molecular Field Analysis. Drug Des. & Disc., 1999, 16, 55-76.
14. Bohm, M.; Sturzebecher, J.; Klebe, G. Three-Dimensional Structure Activity Analysis Using Comparative Molecular Field Analysis and Comparative Similarity Indicies Analysis to Elucidate Selectivity Differences of Inhibitors Binding to Trypsin, Thrombin and Factor Xa, J. Med. Chem., 1999, 42, 458-477.
15. 2 Dopamine Receptors. J. Med. Chem. 1998, 41, 4385-4399.
16. Gokhale, V. M.; Kulkarni, V. M. Comparative Molecular Field Analysis of Fungal Squalene Epoxidase Inhibitors. J. Med. Chem., 1999, in press.
17. Kulkarni, S. S.; Kulkarni, V. M. Three-Dimensional Quantitative Structure-Activity Relationship of Interleukin 1-beta Converting Enzvme Inhibitors: A Comparative Molecular Field Analysis Study. J. Med. Chem. 1999, 42, 373-380.
18. Kim, K. H.; Greco, G.; Novellino, E. A Critical Review of Recent CoMFA Applications, Prespectives in Drug Discovery and Design, 1998, 12/13/14, 257-315, Kluwer Academic Publishers.
19. For an excellent discussion of QSAR and the LOO method, see Tong, W.; Lowis, D. R.; Perkins, R.; Chen, Y.; Welsh, W. J.; Goddette, D. W.; Heritage, T. W.; Sheehan, D. M. Evaluation of Quantitative Structure-Activity Relationship Methods for Large-Scale Prediction of Chemicals Binding to the Estrogen Receptor. J. Chem. Inf. Comput. Sci. 1998, 38, 669-677.
20. Bush, B. L.; Nachbar, R. B. Sample-Distance Partial Least Squares: PLS Optimized for Many Variables, with Application to comfier. J. Comput.-Aided Mol. Des. 1993, 7, 587-619.
21. Cramer III, R. D.; Bunce, J. D.; Patterson, D. E. Crossvalidation, Bootstrapping, and Partial Least Squares Compared with Multiple Regression in Convential QSAR Studies. Quant. Struct.-Act. Relat. 1988, 7, 18-25.
22. Dunn, W. J.; Wold, S.; Edlund, U.; Helberg, S. Multivariate Structure-Activity Relationships Between Data from a Battery of Biological Tests and an Ensemble of Structure Descriptors: The PLS Method. Quant. Struct.-Act. Relat. 1984, 3, 131-137.
23. Douguet D.; Thoreau, E.; Grassy, G. Quantitative Structure-Activity Relationship Studies of RAR α, β, γ Retiniod Agonists. Quant. Struct.-Act. Relat., 1999, 18, 107-123.
24. Podlogar, B. L.; Poda, G. I.; Demeter, D. A.; Zhang, S.; Carson, J. R.; Nielson, L. A.; Reitz, A. B.; Ferguson, D. M. Synthesis and Evaluation of 4-(N,N-Diarylamino)piperidines with High Selectivity to the δ-Opioid Receptor' A Combined 3D-QSAR and Ligand Docking Study. Drug Des. and Disc. 2000, xx,xx-xx.
25. 2-Adrenoceptor: The Development of New, Highly Selective Inhibitors of PNMT. Bioorg. Med. Chem. Lett., 1999, 9, 481-486.
26. Medvedev, A. E.; Veselovsky, A. V.; Shvedov, V. I.; Tikhonova, O. V.; Moskvitina, T. A.; Fedotova, O. A.; Axenova, L. N.; Kamyshanskaya, N. S.; Kirkel, A. Z; Ivanov, A. S. Inhibition of Monoamine Oxidase by Pirlindole Analogues: 3D-QSAR and CoMFA Analysis. J. Chem. Inf. Comput. Sci. 1998, 38, 1137-1144.
27. 2c) Affinities: Synthesis, Pharmacology, 3D-QSAR and Molecular Modeling of (Aminoalkyl)benzo- and ñthienocycloalkanones as Putative Atypical Antipsycotics. J. Med. Chem , 1999, 42, 2774-2797.
28. Bromidge, S. M.; Dabbs, S.; Davies, D. T.; Duckworth, D. M.; Forbes, I. T.; Ham, P.; Jones, G. E ; King, F. D.; Saunders, D. V.; Starr, S., Thewlis, K. M.; Wvman, P. A.; Blaney, F. E.; Naylor, C. B.; Bailey, F.; Blackburn, T. P.; Holland, V.; Kennett, G. A.; Riley, G. J., Wood, M. D. Novel and Selective 5-HT2O2B Receptor Antagonists as Potential Anxiolytic Agents: Synthesis, Quantitative Structure-Activity Relationships, and Molecular Modeling of Substituted 1-(3-pyndylcarbamoyl)indolines J. Med. Chem. 1998, 41, 1598-1612.
29. Muszvnski, I. C.; Scapozza, L.; Kovar, K.-A.; Folkers, G. Quantitative Structure-Activity Relationships of Phenyltropanes as Inhibitors of Three Monoamine Transporters: Classical and CoMFA Studies. Quant Struct.-Act. Relat., 1999, 18, 342-353.
30. Xing, L.; Welsh, W. J.; Tong, W.; Perkins, R.; Sheehan, D. M. Comparison of Estrogen Receptor a and b Subtypes Based on Comparative Molecular Field Analysis (CoMFA). SAR and QSAR in Environ. Res., 1999, 10, 215-237.
31. Matter, H.; Schwab, W. Affinity and Selectivity of Matrix Metallo-proteinase Inhibitors: a Chemometrical Study from the Perspective of Ligands and Proteins, J. Med. Chem. 1999, 42, 4506-4523.
32. Langer, T. Molecular Simularity Characterization Using CoMFA. Perspectives in Drug Discovery and Design, 1998, 12-14, 215-231.
33. Kim, K. H. Building a Bridge Between G-Protein-Coupled Receptor Modeling, Protein Crystallography and 3D QSAR Studies for Ligand Design. Prespectives in Drug Discovery and Design, 1998, 12/13/14, 233-255, Kluwer Academic Publishers.
34. 3 Adenosine Receptor Antagonists. J. Med. Chem., 1999, 42, 706-721.
35. Swaan, P. W.; Koops, B. C.; Moret, E. E.; Tukker, J. J Mapping the Binding Site of the Small Intestinal Peptide Carrier (PepT1) Using Comparative Molecular Field Analysis. Receptors Channels 1998, 6, 189-200.