The acid-base profile of a contemporary set of drugs: Implications for drug discovery

SAR and QSAR in Environmental Research

Volumn 20, Issue 7-8, 2009, Pages 611-655

  Manallack, D T ^a  

^a MONASH UNIVERSITY   (Australia)

Author keywords

ADME; Drug discovery; Drug like; Drugs; Ionization constant; Lead like; pKa

Indexed keywords

IONIZATION;

ACID BASE; ADME; CENTRAL NERVOUS SYSTEMS; DRUG; DRUG DISCOVERY; DRUG-LIKE; IONIZABLE GROUPS; IONIZATION CONSTANT; LEAD-LIKE; PKA;

NEUROPHYSIOLOGY;

EID: 72149131439     PISSN: 1062936X     EISSN: 1029046X     Source Type: Journal    
DOI: 10.1080/10629360903438313     Document Type: Article

References (43)

1. T. Hou, J. Wang, W. Zhang, W. Wang, and X. Xu, Recent advances in computational prediction of drug absorption and permeability in drug discovery, Curr. Med. Chem. 13 (2006), pp. 2653-2667.
2. M.S. Lajiness, M. Vieth, and J. Erickson, Molecular properties that influence oral drug-like behavior, Curr. Opin. Drug Discov. Devel. 7 (2004), pp. 470-477.
3. C.A. Lipinski, F. Lombardo, B.W. Dominy, and P.J. Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Del. Rev. 46 (1997), pp. 3-26.
4. T.I. Oprea, A.M. Davis, S.J. Teague, and P.D. Leeson, Is there a difference between leads and drugs? A historical perspective, J. Chem. Inf. Comput. Sci. 41 (2001), pp. 1308-1315.
5. J.R. Proudfoot, Drugs, leads, and drug-likeness: An analysis of some recently launched drugs, Bioorg. Med. Chem. Lett. 12 (2002), pp. 1647-1650.
6. S.J. Teague, A.M. Davis, P.D. Leeson, and T. Oprea, The design of leadlike combinatorial libraries, Angew. Chem. Int. Ed. Engl. 38 (1999), pp. 3743-3748.
7. G.W. Bemis and M.A. Murcko, The properties of known drugs. 1. Molecular frameworks, J. Med. Chem. 39 (1996), pp. 2887-2893.
8. G.W. Bemis and M.A. Murcko, Properties of known drugs. 2. Side chains, J. Med. Chem. 42(1999), pp. 5095-5099.
9. Ajay, G.W. Bemis, and M.A. Murcko, Designing libraries with CNS activity, J. Med. Chem. 42 (1999), pp. 4942-4951.
10. Ajay, W.P. Walters, and M.A. Murcko, Can we learn to distinguish between "drug-like" and "nondrug-like" molecules?, J. Med. Chem. 41 (1998), pp. 3314-3324.
11. D.E. Clark and S.D. Pickett, Computational methods for the prediction of 'drug-likeness', Drug Discov. Today 5 (2000), pp. 49-58.
12. G.M. Keseru, L. Molnar, and I. Greiner, A neural network based virtual high throughput screening test for the prediction of CNS activity, Comb. Chem. High Throughput Screen. 3(2000), pp. 535-540.
13. J. Sadowski and H. Kubinyi, A scoring scheme for discriminating between drugs and nondrugs, J. Med. Chem. 41 (1998), pp. 3325-3329.
14. A.L. Hopkins and A. Polinsky, Knowledge and intelligence in drug design, in Annual Reports in Medicinal Chemistry, Vol. 41, A. Wood, ed., Elsevier, New York, 2006, pp. 425-437.
15. A. Avdeef, Physicochemical profiling (solubility, permeability and charge state), Curr. Top. Med. Chem. 1 (2001), pp. 277-351.
16. A. Avdeef, Absorption and Drug Development: Solubility, Permeability, and Charge State, Wiley, Hoboken, 2003.
17. E.H. Kerns and L. Di, Physicochemical profiling: Overview of the screens, Drug Discov. Today: Technologies 1 (2004), pp. 343-348.
18. Y.C. Martin, A bioavailability score, J. Med. Chem. 48 (2005), pp. 3164-3170.
19. B.G. Katzung (ed.), Basic and Clinical Pharmacology, McGraw-Hill Professional, London, 2004.
20. J. Comer and K. Tam, Lipophilicity profiles, in Pharmacokinetic Optimization in Drug Research: Biological, Physicochemical and Computational Strategies, B. Testa, H. van de Waterbeemd, G. Folkers, and R. Guy, eds., Wiley, Zurich, 2001, pp. 275-304.
21. H. Fischer, R. Gottschlich, and A. Seelig, Blood-brain barrier permeation: Molecular parameters governing passive diffusion, J. Membr. Biol. 165 (1998), pp. 201-211.
22. T. Mitchell, Personal communication.
23. J.I. Wells, Pharmaceutical Preformulation, Ellis Hoowood Ltd., London, 1998.
24. D.A. Williams, - values for some drugs and miscellaneous organic acids and bases, in Foye's Principles of Medicinal Chemistry, D.A. Williams and T.L. Lemke, eds., Lippincott, Williams and Wilkins, Philadelphia, 2002, pp. 1070-1079.
25. D.T. Manallack, The pKa distribution of drugs: Application to drug discovery, Persp. Med. Chem. 2007:1 (2007), pp. 25-38.
26. Australian Medicines Handbook, Australian Medicines Handbook Pty. Ltd., Adelaide, 2008.
27. ACD/pKa DB 9.0, Advanced Chemistry Development, Inc., Toronto, Canada, 2007; software information available at www.acdlabs.com.
28. R.J. Prankerd (ed.), Profiles of Drug Substances, Excipients, and Related Methodology: Volume 33, Elsevier Academic Press, Amsterdam, 2007.
29. R.J. Prankerd, Personal communication.
30. U. Norinder and M. Haeberlein, Computational approaches to the prediction of the blood-brain distribution, Adv. Drug Deliv. Rev. 54 (2002), pp. 291-313.
31. L.C. Chang, J.K. von Frijtag Drabbe Kunzel, T. Mulder-Krieger, R.F. Spanjersberg, S.F. Roerink, G. van den Hout, M.W. Beukers, J. Brussee, and A.P. Ijzerman, A series of ligands displaying a remarkable agonistic-antagonistic profile at the adenosine A1 receptor, J. Med. Chem. 48 (2005), pp. 2045-2053.
32. S. Sweetman, Martindale: The Complete Drug Reference, 35th ed., The Pharmaceutical Press, London, 2006.
33. World Health Organization, Essential medicines list, 2005, Available at http://www.who.int/medicines/publications/essentialmedicines/en/, http://whqlibdoc.who.int/hq/2005/a87017_eng.pdf.
34. The World Drug Index, available from Derwent Information, London, U.K. www.derwent.com.
35. A. Pagliara, P.A. Carrupt, G. Caron, P. Gaillard, and B. Testa, Lipophilicity profiles of ampholytes, Chem. Rev. 97 (1997), pp. 3385-3400.
36. G.L. Holliday, D.E. Almonacid, G.J. Bartlett, N.M. O'Boyle, J.W. Torrance, P. Murray-Rust, J.B. Mitchell, and J.M. Thornton, MACiE (Mechanism, Annotation and Classification in Enzymes): Novel tools for searching catalytic mechanisms, Nucleic Acids Res. 35 (2007), pp. D515-520.
37. J.P. Overington, B. Al-Lazikani, and A.L. Hopkins, How many drug targets are there?, Nat. Rev. Drug Discov. 5 (2006), pp. 993-996.
38. E.S. Huang, Construction of a sequence motif characteristic of aminergic G protein-coupled receptors, Protein Sci. 12 (2003), pp. 1360-1367.
39. M. Hann, B. Hudson, X. Lewell, R. Lifely, L. Miller, and N. Ramsden, Strategic pooling of compounds for high-throughput screening, J. Chem. Inf. Comput. Sci. 39 (1999), pp. 897-902.
40. M.M. Hann and T.I. Oprea, Pursuing the leadlikeness concept in pharmaceutical research, Curr. Opin. Chem. Biol. 8 (2004), pp. 255-263.
41. T. Wunberg, M. Hendrix, A. Hillisch, M. Lobell, H. Meier, C. Schmeck, H. Wild, and B. Hinzen, Improving the hit-to-lead process: Data-driven assessment of drug-like and lead-like screening hits, Drug Discov. Today 11 (2006), pp. 175-180.
42. J.C. Shelley, A. Cholleti, L.L. Frye, J.R. Greenwood, M.R. Timlin, and M. Uchimaya, Epik: A software program for pK(a) prediction and protonation state generation for drug-like molecules, J. Comput. Aided Mol. Des. 21 (2007), pp. 681-691.
43. S. Jelfs, P. Ertl, and P. Selzer, Estimation of pKa for druglike compounds using semiempirical and information-based descriptors, J. Chem. Inf. Model. 47 (2007), pp. 450-459.