Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings

Advanced Drug Delivery Reviews

Volumn 23, Issue 1-3, 1997, Pages 3-25

  Lipinski, Christopher A ^a   Lombardo, Franco ^a   Dominy, Beryl W ^a   Feeney, Paul J ^a  

^a PFIZER INC   (United States)

Author keywords

computational alert; H bond donors and acceptors; MLogP; MWT; poor absorption or permeation; rule of 5; solubility calculation; thermodynamic solubility; turbidimetric solubility

Indexed keywords

CALCULATIONS; COMPUTATIONAL METHODS; DRUG THERAPY; ESTIMATION; HYDROGEN BONDS; MOLECULAR WEIGHT; SOLUBILITY; THERMODYNAMIC PROPERTIES;

COMPUTATIONAL ALERT; DISCOVERY SETTING; DRUG DISCOVERY; HIGH THROUGHPUT SCREENING; HYDROGEN BOND ACCEPTORS; HYDROGEN BOND DONORS; MORIGUCHI LOG P; POOR ABSORPTION; POOR PERMEATION; TURBIDIMETRIC SOLUBILITY;

DRUG PRODUCTS;

ACICLOVIR; ALPRAZOLAM; ATENOLOL; AZITHROMYCIN; CAFFEINE; CAPTOPRIL; CARBAMAZEPINE; CHLORAMPHENICOL; CIMETIDINE; CLONIDINE; CYCLOSPORIN; DESIPRAMINE; DIAZEPAM; DICLOFENAC; DILTIAZEM; DOXORUBICIN; ENALAPRIL; ERYTHROMYCIN; FAMOTIDINE; FELODIPINE; FLUOROURACIL; FLURBIPROFEN; FUROSEMIDE; IBUPROFEN; IMIPRAMINE; UNINDEXED DRUG; ZIDOVUDINE;

ABSORPTION; COMPUTER PROGRAM; DRUG DEVELOPMENT; ENERGY; HYDROGEN BOND; METHODOLOGY; MODEL; MOLECULAR WEIGHT; PARTITION COEFFICIENT; PERMEABILITY; PHYSICAL CHEMISTRY; PREDICTION; PRIORITY JOURNAL; REVIEW; SCREENING; SOLUBILITY; THERMODYNAMICS; TURBIDIMETRY;

EID: 0031024171     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0169-409X(96)00423-1     Document Type: Review

References (50)

1. Kubinyi, H. (1995) Strategies and recent technologies in drug discovery. Pharmazie 50, 647-662.
2. Moos, W.H. and Green, G.D. (1993) Chapter 33. Recent Advances in the Generation of Molecular Diversity. Annu. Rep. Med. Chem. 28, 315-324.
3. Patel, D.V. and Gordon, E.M. (1996) Applications of small-molecule combinatorial chemistry to drug discovery. Drug Discov. Today 1, 134-144.
4. Baum, R.M. (1994) Combinatorial approaches provide fresh leads for medicinal chemistry. Chem. Eng. News February 7, 20-26.
5. Chow, H., Chen, H., Ng, T., Nyrdal, P. and Yalkowski, S.H. (1995) Using backpropagation networks for the estimation of aqueous activity coefficients of aromatic compounds. J. Chem. Inf. Comput. Sci., 35, 723-728.
6. Andrews, P.R., Craik, DJ. and Martin, J.L. (1984) Functional group contributions to drug-receptor interactions. J. Med. Chem. 27, 1648-1657.
7. Navia, M.A. and Chaturvedi, P.R. (1996) Design principles for orally bioavailable drugs. Drug. Dev. Today 1, 179-189.
8. Pardridge, W.M. (1995) Transport of small molecules through the blood-brain barrier: biology and methodology. Adv. Drug Deliv. Rev. 15, 5-36.
9. Cohen, B.E. and Bangham, A.D. (1972) Diffusion of small non-electrolytes across liposome membranes. Nature 236, 173-174.
10. Testa, B., Carrupt, P-A., Gaillard, P., Billois, F. and Weber, P. (1996) Lipophilicity in molecular modelling. Pharm. Res. 13, 335-343.
11. Moriguchi, I., Hirono, S., Liu, Q., Nakagome, Y. and Matsushita, Y. (1992) Simple method of calculating octanol/ water partition coefficient. Chem. Pharm. Bull. 40, 127-130.
12. Moriguchi, I., Hirono, S., Nakagome, I. and Hirano, H. (1994) Comparison of log P values for drugs calculated by several methods. Chem. Pharm. Bull. 42, 976-978.
13. Leo, A.J. (1995) Critique of recent comparison of log P calculation methods. Chem. Pharm. Bull. 43, 512-513.
14. Abraham, M.H., Chadha, S.H., Whiting, G.S. and Mitchell, R.C. (1994) Hydrogen bonding. 32. An analysis of water-octanol and water-alkane partitioning and the delta log P parameter of Seiler. J. Pharm. Sci. 83, 1085-1100.
15. Paterson, D.A., Conradi, R.A., Hilgers, A.R., Vidmar, T.J. and Burton, P.S. (1994) A non-aqueous partitioning system for predicting the oral absorption potential of peptides. Quant. Struct.-Act. Relatsh. 13, 4-10.
16. Hillgren, K.M., Kato, A. and Borchardt, R.T. (1995) In vitro systems for studying intestinal drug absorption. Med. Res. Rev. 15, 83-109.
17. Abraham, M.H. (1993) Hydrogen bonding. 31. Construction of a scale of solute effective or summation hydrogen-bond basicity. J. Phys. Org. Chem. 6, 660-684.
18. Raevsky, O.A., Grigor'ev, V.Y., Kireev, D.B. and Zefirov, N.S. (1992) Complete thermodynamic description of H-bonding in the framework of multiplicative approach. Quant. Struct.-Act. Relatsh. 11, 49-63.
19. Raevsky, O.A., Schaper, K-J. and Seydel, J.K. (1995) H-Bond contribution to octanol-water partition coefficients of polar compounds. Quant. Struct.-Act. Relatsh. 14, 433-436.
20. Lipinski, C.A. (1995) Computational alerts for potential absorption problems: profiles of clinically tested drugs. In: Tools for Oral Absorption. Part Two. Predicting Human Absorption. BIOTEC, PDD symposium, AAPS, Miami.
21. Prediction of Drug Transport Through Membranes. Chicago IAM Meeting, August 18, 1995.
22. Workshop on Oral Drug Delivery: Interface Between Discovery and Development. Report and Recommendations. National Institutes of Health, National Institute of General Medical Sciences. Herndon, Virginia, December 5-7, 1993.
23. Lipinski, C.A., Davis, A.L., Aldridge, P.K. and Brown, C.W. (1994) Biologically relevant UV-based solubility assays. Pharmaceutical Analysis Session, 45th Pittsburgh Conf., Chicago, Oral Presentation 959.
24. Reichardt, C. (1988) Solvents and Solvent Effects in Organic Chemistry. 2nd edn. VCH, Weinheim, pp. 27-35.
25. Bodor, N., Harget, A. and Huang, N.-J. (1991) Neural network studies. 1. Estimation of the aqueous solubility of organic compounds. J. Am. Chem. Soc. 113, 9480-9483.
26. Gavezzotti, A. (1994) Are crystal structures predictable? Acc. Chem. Res. 27, 309-314.
27. Polymorph Predictor, Molecular Simulations Inc., Burlington, MA.
28. Abraham, M.H. (1993) Scales of solute hydrogen-bonding: their construction and application to physicochemical and biochemical processes. Chem. Soc. Rev. 22, 73-83.
29. Abraham, M.H. and McGowan, J.C. (1987) The use of characteristic volumes to measure cavity terms in reversed phase liquid chromatography. Chromatographia 23, 243-246.
30. Taft, R.W., Abraham, N.H., Doherty, R.M. and Kamlet, M.J. (1985) The molecular properties governing solubilities of organic nonelectrolytes in water. Nature 315, 384-386.
31. Kamlet, M.J. (1993) Linear solvation energy relationships: an improved equation for correlation and prediction of aqueous solubilities of aromatic solutes including polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Prog. Phys. Org. Chem. 19, 295-317.
32. Abraham, M.H., Chadha, H.S. and Mitchell, R.C. (1994) Hydrogen bonding. 33. Factors that influence the distribution of solutes between blood and brain. J. Pharm. Sci. 83, 1257-1268.
33. Brinck, T., Murray, J.S. and Politzer, P. (1993) Octanol/ water partition coefficients expressed in terms of solute molecular surface areas and electrostatic potentials. J. Org. Chem. 58. 7070-7073.
34. Murray, J.S. and Politzer, P. ( 1991 ) Correlations between the solvent hydrogen-bond-donating parameter α and the calculated molecular surface electrostatic potential. J. Org. Chem. 56, 6715-6717.
35. Murray, J.S., Ranganathan, S. and Politzer, P. (1991) Correlations between the solvent hydrogen bond acceptor parameter β and the calculated molecular electrostatic potential. J. Org. Chem. 56, 3734-3737.
36. Famini, G.R., Penski, C.A. and Wilson, L.Y. (1992) Using theoretical descriptors in quantitative structure activity relationships: some physicochemical properties. J. Phys. Org. Chem. 5, 395-408.
37. Headley, A.D., Starnes, S.D., Wilson, L.Y. and Famini, G.R. (1994) Analysis of solute/solvent interactions for the acidity of acetic acids by theoretical descriptors. J. Org. Chem. 59, 8040-8046.
38. Ruelle, P., Sarraf, E. and Kesselring, U.W. (1994) Prediction of carbazole solubility and its dependence upon the solvent nature. Int. J. Pharm. 104, 125-133.
39. Ruelle, P., Rey-Mermet, C., Buchmann, M., Nam-Tran, H., Kesselring, U.W. and Huyskens, P.L. (1991) A new predictive equation for the solubility of drugs based on the thermodynamics of mobile disorder. Pharm. Res. 8, 840-850.
40. Ruelle, P. and Kesselring, U.W. (1994) Solubility predictions for solid nitriles and tertiary amides based on the mobile order theory. Pharm. Res. 11, 201-205.
41. Yalkowski, S.H. and Valvani, S.C. (1980) Solubility and partitioning 1: solubility of nonelectrolytes in water. J. Pharm. Sci. 69, 912-922.
42. Abramovitz, R. and Yalkowski, S.H. (1990) Estimation of aqueous solubility and melting point of PCB congeners. Chemosphere 21, 1221-1229.
43. Yalkowski, S.H. and Pinal, R. (1993) Estimation of the solubility of complex organic compounds. Chemosphere 26, 1239-1261.
44. Leo, A. (1993) Calculating log Poet from structures. Chem. Rev. 93, 1281-1306 (CLOGP version 3.5).
45. Abramovitz, R. and Yalkowski, S.H. (1990) Melting point, boiling point, and symmetry. Pharm. Res. 7, 942-947.
46. Dannenfelser, R.M., Surendran, N. and Yalkowski, S.H. (1993) Molecular symmetry and related properties. SAR & QSAR Environ. Res. 1, 273-292.
47. Suzuki, T. (1991) Development of an automatic estimation system for both the partition coefficient and aqueous solubility. J. Comput. Aided Mol. Des. 5, 149-166 (CHEMICALC-2, v. 1.0).
48. Myrdal, P.B., Manka, A.M. and Yalkowsky, S.H. (1995) Aquafac 3: aqueous functional group activity coefficients; application to the estimation of aqueous solubility. Chemosphere 30, 1619-1637.
49. Bodor, N. and Huang, M.-J. (1992) A new method for the estimation of the aqueous solubility of organic compounds. J. Pharm. Sci. 81, 954-959.
50. Nelson, T.M. and Jurs, P.C. (1994) Prediction of aqueous solubility of organic compounds. J. Chem. Inf. Comput. Sci. 34, 601-609.