Quantitative structure-metabolism relationships: Steric and nonsteric effects in the enzymatic hydrolysis of noncongener carboxylic esters

Journal of Medicinal Chemistry

Volumn 42, Issue 25, 1999, Pages 5160-5168

  Buchwald, Peter ^a   Bodor, Nicholas ^a  

^a UNIVERSITY OF FLORIDA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ESTER; HYDROLASE;

ARTICLE; BLOOD; CALCULATION; CHEMICAL STRUCTURE; ENZYME ACTIVITY; HUMAN; HYDROLYSIS; IN VITRO STUDY; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

CARBOXYLIC ACIDS; CARBOXYLIC ESTER HYDROLASES; ESTERS; HALF-LIFE; HUMANS; HYDROLYSIS; PHARMACOKINETICS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033576649     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990145k     Document Type: Article

References (105)

1. Augustinsson, K.-B. Multiple forms of esterase in vertebrate blood plasma. Ann. N.Y. Acad. Sci. 1961, 94, 844-860.
2. Krisch, K. Carboxylic ester hydrolases. In The Enzymes; Boyer, P. D., Ed.; Academic Press: New York, 1971; Vol. 5, pp 43-69.
3. Heymann, E. Hydrolysis of carboxylic esters and amides. In Metabolic Basis of Detoxication; Jakoby, W. B., Bend, J. R., Caldwell, J., Eds.; Academic Press: New York, 1982; pp 229-245.
4. Walker, C. H.; Mackness, M. I. Esterases: Problems of identification and classification. Biochem. Pharmacol. 1983, 32, 3265-3569.
5. Williams, F. W. Clinical significance of esterases in man. Clin. Pharmacokin. 1985, 10, 392-403.
6. Leinweber, F.-J. Possible physiological roles of carboxylic ester hydrolases. Drug Metabol. Rev. 1987, 18, 379-439.
7. Satoh, T.; Hosokawa, M. The mammalian carboxylesterases: from molecules to functions. Annu. Rev. Pharmacol. Toxicol. 1998, 38, 257-288.
8. Quon, C. Y.; Mai, K.; Patil, G.; Stampfli, H. F. Species differences in the stereoselective hydrolysis of esmolol by blood esterases. Drug Metab. Dispos. 1988, 16, 425-428.
9. Minagawa, T.; Kohno, Y.; Suwa, T.; Tsuji, A. Species differences in hydrolysis of isocarbacyclin methyl ester (TEI-9090) by blood esterases. Biochem. Pharmacol. 1995, 49, 1361-1365.
10. Chappell, W. R.; Mordenti, J. Extrapolation of lexicological and pharmacological data from animals to humans. Adv. Drug Res. 1991, 20, 1-116.
11. Campbell, D. B. Extrapolation from animals to man. The integration of pharmacokinetics and pharmacodynamics. Ann. N.Y. Acad. Sci. 1996, 801, 116-135.
12. Quon, C. Y.; Stampfli, H. F. Biochemical properties of blood esmolol esterase. Drug Metab. Dispos. 1985, 13, 420-424.
13. Feldman, P. L.; James, M. K.; Brackeen, M. F.; Bilotta, J. M.; Schuster, S. V.; Lahey, A. P.; Lutz, M. W.; Johnson, M. R.; Leighton, H. J. Design, synthesis, and pharmacological evaluation of ultrashort-to long-acting opioid analgetics. J. Med. Chem. 1991, 34, 2202-2208.
14. Stampfli, H. F.; Quon, C. Y. Polymorphic metabolism of flestolol and other ester containing compounds by a carboxylesterase in New Zealand white rabbit blood and cornea. Res. Commun. Mol. Pathol. Pharmacol. 1995, 88, 87-97.
15. Kam, S.-T.; Matier, W. L.; Mai, K. X.; Barcelon-Yang, C.; Borgman, R. J.; O'Donnell, J. P.; Stampfli, H. F.; Sum, C. Y.; Anderson, W. G.; Gorczynski, R. J.; Lee, R. J. [(Arylcarbonyl)-oxy]propanolamines. 1. Novel β-blockers with ultrashort duration of action. J. Med. Chem. 1984, 27, 1007-1016.
16. Graffher-Nordberg, M.; Sjödin, K; Tunek, A.; Hallberg, A. Synthesis and enzymatic hydrolysis of esters, constituting simple models of soft drugs. Chem. Pharm. Bull. 1998, 46, 591-601.
17. Higuchi, T.; Davis, S. S. Thermodynamic analysis of structure-activity relationships of drugs: Prediction of optimal structure. J. Pharm. Sci. 1970, 59, 1376-1383.
18. Purcell, W. P.; Bass, G. E.; Clayton, J. M. Strategy to Drug Design: A Guide to Biological Activity; Wiley-Interscience: New York, 1973.
19. Hansch, C.; Leo, A. J. Substituent Constants for Correlation Analysis in Chemistry and Biology; Wiley-Interscience: New York, 1979.
20. Hansch, C.; Leo, A.; Hoekman, D. Exploring QSAR. Hydrophobie, Electronic, and Steric Constants; American Chemical Society: Washington, DC, 1995; Vol. 2.
21. Kubinyi, H. The quantitative analysis of structure-activity relationships. In Burger's Medicinal Chemistry and Drug Discovery; Wolff, M. E., Ed.; Wiley-Interscience: New York, 1995; Vol. 1, pp 497-571.
22. Dittert, L. W.; Caldwell, H. C.; Ellison, T.; Irwin, G. M.; Rivard, D. E.; Swintosky, J. V. Carbonate ester prodrugs of salicylic acid. J. Pharm. Sci. 1968, 57, 828-831.
23. Wechter, W. J.; Johnson, M. A.; Hall, C. M.; Warner, D. T.; Berger, A. E.; Wenzel, A. H.; Gish, D. T.; Neil, G. L. ara-Cytidine acylates. Use of drug design predictors in structure-activity relationship correlations. J. Med. Chem. 1975, 18, 339-344.
24. Wagner, J.; Grill, H.; Henschler, D. Prodrugs of etilefrine: Synthesis and evaluation of 3′-(O-acyl) derivatives. J. Pharm. Sci. 1980, 69, 1423-1427.
25. Patel, J. P.; Repta, A. J. Enol esters as potential pro-drugs. II. In vitro aqueous stability and enzyme-mediated hydrolysis of several enol esters of acetophenone. Int. J. Pharm. 1981, 29, 29-47.
26. Hattori, K.; Kamio, M.; Nakajima, E.; Oshima, T.; Satoh, T.; Kitagawa, H. Characterization of steroid hormone ester hydrolyzing enzymes in liver microsomes. Biochem. Pharmacol. 1981, 30, 2051-2056.
27. Maksay, G.; Ötvös, L. Activation of prodrugs: Structure-pharmacokinetic correlations of benzodiazepine esters. Drug Metab. Rev. 1983, 14, 1165-1192.
28. Kawaguchi, K.; Suzuki, Y.; Nakahara, Y.; Nambu, N.; Nagai, T. Activity of esterase in the hydrolysis of 3′,5′-diesters of 5-fluoro-2′-deoxyuridine in relation to the structure of the diester prodrugs. Chem. Pharm. Bull. 1985, 33, 301-307.
29. Anderson, B. D.; Conradi, R. A.; Spilman, C. H.; Forbes, A. D. Strategies in the design of solution-stable, water-soluble prodrugs. III. Influence of the pro-moiety on the bioconversion of 21-esters of corticosteroids. J. Pharm. Sci. 1985, 74, 382-387.
30. van de Waterbeemd, H.; Testa, B.; Marrel, C.; Cooper, D. R.; Jenner, P.; Marsden, C. D. Multivariate statistical analysis of L-DOPA esters as potential anti-Parkinsonian prodrugs. Drug Des. Deliv. 1987, 2, 135-143.
31. Bundgaard, H.; Fakh, E.; Larsen, C.; Mosher, G. L.; Mikkelson, T. J. Pilocarpine prodrugs. II. Synthesis, bioconversion, and physicochemical properties of sequentially labile pilocarpine acid diesters. J. Pharm. Sci. 1986, 75, 775-783.
32. Bundgaard, H.; Buur, A.; Chang, S.-C.; Lee, V. H. L. Timolol prodrugs: synthesis, stability and lipophilicity of various alkyl, cycloalkyl and aromatic esters of timolol. Int. J. Pharm. 1988, 46, 77-88.
33. Nielsen, N. M.; Bundgaard, H. Prodrugs as drug delivery systems. 68. Chemical and plasma-catalyzed hydrolysis of various esters of benzoic acid: a reference system for designing prodrug esters of carboxylic acid agents. Int. J. Pharm. 1987, 39, 75-85.
34. Nielsen, N. M.; Bundgaard, H. Evaluation of glycolamide esters and various other esters of aspirin as true aspirin prodrugs. J. Med. Chem. 1989, 32, 727-734.
35. Bodor, N.; El-Koussi, A.; Kano, M.; Khalifa, M. M. Soft drugs. 7. β-Blockers for systemic and ophthalmic use. J. Med. Chem. 1988, 31, 1651-1656.
36. Altomare, C.; Carotti, A.; Cellamare, S.; Ferappi, M.; Cagiano, R.; Renna, G. QSAR analysis of chemical and serum-catalyzed hydrolysis of phenyl ester prodrugs of nipecotic acid. Int. J. Pharm. 1988, 48, 91-102.
37. Stout, D. M.; Black, L. A.; Barcelon-Yang, C.; Matier, W. L.; Brown, B. S.; Quon, C. Y.; Stampfli, H. F. Ester derivatives of 2,6-bis(1-pyrrolidinylmethyl)-4-benzamidophenol as short-acting antiarrhythmic agents. 1. J. Med. Chem. 1989, 32, 1910-1913.
38. Chorvat, R. J.; Black, L. A.; Ranade, V. V.; Barcelon-Yang, C.; Stout, D. M.; Brown, B. S.; Stampfli, H. F.; Quon, C. Y. Monoand bis(aminomethyl)phenylacetic acid esters as short-acting antiarrhythmic agents. 2. J. Med. Chem. 1993, 36, 2494-2498.
39. Durrer, A.; Walther, B.; Racciatti, A.; Boss, G.; Testa, B. Structure-metabolism relationships in the hydrolysis of nicotinate esters by rat liver and brain subcellular fractions. Pharm. Res. 1991, 8, 832-839.
40. Durrer, A.; Wernly-Chung, G. N.; Boss, G.; Testa, B. Enzymic hydrolysis of nicotinate esters: comparison between plasma and liver catalysis. Xenobiotica 1992, 22, 273-282.
41. Yang, H.-S.; Wu, W.-M.; Bodor, N. Soft drugs. XX. Design, synthesis and evaluation of ultra-short acting beta-blockers. Pharm. Res. 1995, 12, 329-336.
42. Baxter, A. J. G.; Carr, R D.; Eyley, S. C.; Fraser-Rae, L.; Hallam, C.; Harper, S. T.; Hurved, P. A.; King, S. J.; Meghani, P. (R)-2-(3-Mercapto-2(S)-methyl-1-oxo-propoxy)-3-(methylthio)propanoic acid, the first ultra-short-acting angiotensin converting enzyme inhibitor. J. Med. Chem. 1992, 35, 3718-3720.
43. Stinchcomb, A. L.; Paliwal, A.; Dua, R.; Imoto, H.; Woodard, R. W.; Flynn, G. L. Permeation of buprenorphine and its 3-alkylester prodrugs through human skin. Pharm. Res. 1996, 13, 1519-1523.
44. Charton, M. Prodrug lability prediction through the use of substituent effects. Methods Enzymol. 1985, 112, 323-340.
45. Bodor, N. Androstene derivatives. U.S. Patent 5 981 517, Nov 9, 1999.
46. Fedtke, N.; Wiegand, H.-J. Hydrolysis of vinyl acetate in human blood. Arch. Toxicol. 1990, 64, 428-429.
47. Cook, C. S.; Karabatsos, P. J.; Schoenhard, G. L.; Karim, A. Species dependent esterase activities for hydrolysis of an anti-HIV prodrug glycovir and bioavalability of active SC-48334. Pharm. Res. 1995, 12, 1158-1164.
48. Bodor, N.; Gabanyi, Z.; Wong, C.-K. A new method for the estimation of partition coefficient. J. Am. Chem. Soc. 1989, 111, 3783-3786.
49. Brewster, M. E.; Huang, M.-J.; Kaminski, J. J.; Pop, E.; Bodor, N. Reactivity of biologically important reduced pyridines. VIII. A semiempirical (AM1) study of the oxidation of 3-substituted-1-methyl-1,4-dihydropyridines. J. Comput. Chem. 1991, 12, 1278-1282.
50. Buchwald, P.; Bodor, N. Molecular size-based model to describe simple organic liquids. J. Phys. Chem. B 1998, 102, 5715-5726.
51. Taft, R. W., Jr. Polar and steric substituent constants for aliphatic and o-benzoate groups from rates of esterification and hydrolysis of esters. J. Am. Chem. Soc. 1952, 74, 3120-3128.
52. Taft, R. W., Jr. Separation of polar, steric, and resonance effects in reactivity. In Steric Effects in Organic Chemistry; Newman, M. S., Ed.; Wiley: New York, 1956; pp 556-675.
53. Charton, M. The nature of the ortho effect. II. Composition of the Taft steric parameters. J. Am. Chem. Soc. 1969, 91, 615-618.
54. Charton, M. The upsilon steric parameter-definition and determination. Top. Curr. Chem. 1983, 114, 57-91.
55. Verloop, A.; Hoogenstraaten, W.; Tipker, J. Development and application of new steric substituent parameters in drug design. In Drug Design; Ariëns, E. J., Ed.; Academic Press: New York, 1976; Vol. VII; pp 165-207.
56. Verloop, A. The STERIMOL Approach to Drug Design; Marcel Dekker: New York, 1987.
57. Fujita, T.; Iwamura, H. Applications of various steric constants to quantitative analysis of structure-activity relationships. Top. Curr. Chem. 1983, 114, 119-157.
58. Silipo, C.; Vittoria, A. Three-dimensional structure of drugs. In Comprehensive Medicinal Chemistry; Hansch, C., Sammes, P. G., Taylor, J. B., Eds.; Pergamon Press: New York, 1990; Vol. 4, pp 153-204.
59. Ingold, C. K. The mechanism of, and constitutional factors controlling, the hydrolysis of carboxylic esters. I. The constitutional significance of hydrolytic stability maxima. J. Chem. Soc. 1930, 1032-1039.
60. Bowden, K.; Young, R. C. Structure-activity relations. I. A series of antagonists of acetylcholine and histamine at the postganglionic receptors. J. Med. Chem. 1970, 13, 225-233.
61. Tolman, C. A. Phosphorus ligand exchange equilibria on zerovalent nickel. A dominant role for steric effects. J. Am. Chem. Soc. 1970, 92, 2956-2965.
62. Tolman, C. A. Steric effects of phosphorus ligands in organometallic chemistry and homogeneous catalysis. Chem. Rev. 1977, 77, 313-348.
63. Seeman, J. I.; Viers, J. W.; Schug, J. C.; Stovall, J. C. Correlation of nonadditive kinetic effects with molecular geometries. Structure and reactivity of alkyl- and cycloalkenylpyridines. J. Am. Chem. Soc. 1984, 106, 143-151.
64. 8. Characteristic feature and comparison with some other steric constants. Tetrahedron 1992, 48, 1539-1556.
65. 8. Its application to the hydrolyses of carboxamides. Chem. Lett. 1993, 725-728.
66. 8 based on molecular mechanics calculations. 2. Directionally weighted steric constants and their application to the analysis of the steric course of reactions. J. Phys. Org. Chem. 1995, 8, 791-798.
67. χb as substituent parameters. Bull. Chem. Soc. Jpn. 1996, 69, 1003-1015.
68. 8). J. Comput. Chem. 1998, 19, 215-221.
69. White, D.; Taverner, B. C.; Leach, P. G. L.; Coville, N. J. Quantification of substituent and ligand size by the use of solid angles. J. Comput. Chem. 1993, 14, 1042-1049.
70. White, D. P.; Leach, P. G. L.; Coville, N. J. Solid angles. 5. Chiral molecules and the case of face selectivity. J. Math. Chem. 1995, 18, 99-114.
71. Taverner, B. C. Improved algorithm for accurate computation of molecular solid angles. J. Comput. Chem. 1996, 17, 1612-1623.
72. Chauvin, R.; Kagan, H. B. Solid angle as steric parameter of acyclic saturated groups. Chirality 1991, 3, 242-253.
73. Gavezzotti, A. The calculation of molecular volumes and the use of volume analysis in the investigation of structured media and of solid-state organic reactivity. J. Am. Chem. Soc. 1983, 105, 5220-5225.
74. Leahy, D. E. Intrinsic molecular volume as a measure of the cavity term in linear solvation energy relationships: octanol-water partition coefficients and aqueous solubilities. J. Pharm. Sci. 1986, 75, 629-636.
75. McGowan, J. C.; Mellors, A. Molecular Volumes in Chemistry and Biology. Application Including Partitioning and Toxicology; Ellis Harwood: Chichester, 1986.
76. Juhász, A.; Huang, F.; Ji, F.; Buchwald, P.; Wu, W.-M.; Bodor, N. Design and evaluation of new soft anticholinergic agents. Drug. Dev. Res. 1998, 43, 117-127.
77. Bader, R. F. W.; Carrol, M. T.; Cheeseman, J. R.; Chang, C. Properties of atoms in molecules: atomic volumes. J. Am. Chem. Soc. 1987, 109, 7968-7979.
78. Leo, A.; Hansch, C.; Elkins, D. Partition coefficients and their uses. Chem. Rev. 1971, 71, 525-616.
79. Taylor, P. J. Hydrophobic properties of drugs. In Comprehensive Medicinal Chemistry; Hansch, C., Sammes, P. G., Taylor, J. B., Eds.; Pergamon Press: New York, 1990; Vol. 4, pp 241-294.
80. Sangster, J. Octanol - Water Partition Coefficients: Fundamentals and Physical Chemistry; Wiley & Sons: Chichester, 1997.
81. Buchwald, P.; Bodor, N. Octanol-water partition: Searching for predictive models. Curr. Med. Chem. 1998, 5, 353-380.
82. oct from structures. Chem. Rev. 1993, 93, 1281-1306.
83. Bodor, N.; Huang, M.-J. An extended version of a novel method for the estimation of partition coefficients. J. Pharm. Sci. 1992, 81, 272-281.
84. Bodor, N.; Buchwald, P. Molecular size based approach to estimate partition properties for organic solutes. J. Phys. Chem. B 1997, 101, 3404-3412.
85. Buchwald, P.; Bodor, N. Octanol-water partition of nonzwitterionic peptides: Predictive power of a molecular size-based model. Proteins 1998, 30, 86-99.
86. Meylan, W. M.; Howard, P. H. Atom/fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sci. 1995, 84, 83-92.
87. Moriguchi, I.; Hirono, S.; Liu, Q.; Nakagome, I.; Matsushita, Y. Simple method of calculating octanol/water partition coefficient. Chem. Pharm. Bull. 1992, 40, 127-130.
88. Bodor, N.; Huang, M.-J. A new method for the estimation of the aqueous solubility of organic compounds. J. Pharm. Sci. 1992, 81, 954-960.
89. Hammett, L. P. The effect of structure upon the reactions of organic compounds. Benzene derivatives. J. Am. Chem. Soc. 1937, 59, 96-103.
90. Hammett, L. P. Physical Organic Chemistry; McGraw-Hill: New York, 1940.
91. Swain, C. G.; Lupton, E. C., Jr. Field and resonance components of substituent effects. J. Am. Chem. Soc. 1968, 90, 4328-4337.
92. Karelson, M.; Lobanov, V. S.; Katritzky, A. R. Quantum-chemical descriptors in QSAR/QSPR studies. Chem. Rev. 1996, 96, 1027-1043.
93. Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. AMI: a new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 1985, 107, 3902-3909.
94. Parr, R. G.; Pearson, R. G. Absolute hardness: companion parameter to absolute electronegativity. J. Am. Chem. Soc. 1983, 105, 7512-7516.
95. Pearson, R. G. Absolute elctronegativity and hardness correlated with molecular orbital theory. Proc. Natl. Acad. Sci. U.S.A. 1986, 83, 8440-8441.
96. Sotomatsu, T.; Murata, Y.; Fujita, T. Correlation-analysis of substituent effects on the acidity of benzoic-acids by the AMI method. J. Comput. Chem. 1989, 10, 94-98.
97. Cocchi, M.; Menziani, M. C.; De Benedetti, P. G.; Cruciani, G. Theoretical versus empirical molecular descriptors in monosubstituted benzenes-a chemometric study. Chemom. Intell. Lab. Sys. 1992, 14, 209-224.
98. Kourounakis, A.; Bodor, N. Quantitative structure activity relationships of catechol derivatives on nerve growth factor secretion in L-M cells. Pharm. Res. 1995, 12, 1199-1204.
99. Dearden, J. C.; Ghafourian, T. Hydrogen bonding parameters for QSAR: Comparison of indicator variables, hydrogen bond counts, molecular orbital and other parameters. J. Chem. Inf. Comput. Sci. 1999, 39, 231-235.
100. Bodor, N.; Buchwald, P. Drug targeting via retrometabolic approaches. Pharmacol. Ther. 1997, 76, 1-27.
101. Bodor, N.; Buchwald, P.; Huang, M.-J. Computer assisted design of new drugs based on retrometabolic concepts. SAR QSAR Environ. Res. 1998, 8, 41-92.
102. Bodor, N.; Buchwald, P.; Huang, M.-J. The role of computational techniques in retrometabolic drug design strategies. In Computational Molecular Biology; Leszczynski, J., Ed.; Elsevier: Amsterdam, 1999; pp 569-618.
103. Bodor, N.; Buchwald, P. Soft drug design: general principles and recent applications. Med. Res. Rev. 2000, in press.
104. Cygler, M.; Schrag, J. D.; Sussman, J. L.; Harel, M.; Silman, I.; Gentry, M. K.; Doctor, B. P. Relationship between sequence conservation and 3-dimensional structure in a large family of esterases, lipases, and related proteins. Protein Sci. 1993, 2, 366-382.
105. Frey, P. A.; Whitt, S. A.; Tobin, J. B. A low-barrier hydrogenbond in the catalytic triad of serine proteases. Science 1994, 264, 1927-1930.