Organic stereochemistry. Part 5: Stereoselectivity in molecular and clinical pharmacology

Helvetica Chimica Acta

Volumn 96, Issue 5, 2013, Pages 747-798

  Testa, Bernard ^a   Vistoli, Giulio ^b   Pedretti, Alessandro ^b   Caldwell, John ^c  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^b UNIVERSITY OF MILAN   (Italy)

^c UNIVERSITY OF LIVERPOOL   (United Kingdom)

Author keywords

Molecular pharmacology; Stereochemistry; Stereoselectivity; Symmetry elements

Indexed keywords

CLINICAL PHARMACOLOGY; DIFFERENTIAL INTERACTION; MOLECULAR PHARMACOLOGY; MUSCARINIC RECEPTOR; ORGANIC STEREOCHEMISTRY; PHARMACOLOGICAL ACTIVITY; PHARMACOLOGICAL EFFECTS; XENOBIOTIC METABOLISM;

ENANTIOMERS; MOLECULAR BIOLOGY; MOLECULAR DYNAMICS; STEREOCHEMISTRY;

STEREOSELECTIVITY;

HYOSCYAMINE; MUSCARINIC RECEPTOR;

CHIRALITY; DRUG ABSORPTION; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG EXCRETION; ENANTIOMER; MOLECULAR DYNAMICS; MOLECULAR MECHANICS; MOLECULAR MODEL; MOLECULAR RECOGNITION; PRIORITY JOURNAL; REVIEW; STEREOCHEMISTRY; XENOBIOTIC METABOLISM;

EID: 84878083930     PISSN: 0018019X     EISSN: 15222675     Source Type: Journal    
DOI: 10.1002/hlca.201200473     Document Type: Review

References (182)

1. 'Chirality in Drug Research', Eds. E. Francotte, W. Lindner, Wiley-VCH, Weinheim, Germany, 2006, 351 p.
2. 'Stereochemical Aspects of Drug Action and Disposition', Eds. M. Eichelbaum, B. Testa, A. Somogyi, Eds, Springer Verlag, Berlin, 2003, 442 p.
3. A. F. Casy, 'The Steric Factor in Medicinal Chemistry-Dissymmetric Probes of Pharmacological Receptors', Plenum Press, New York, 1993, 570 p.
4. 'Biological Asymmetry and Handedness', Eds. G. R. Bock, J. Marsh, Ciba Foundation Symposium 162, John Wiley & Sons, Chichester, 1991, 327 p.
5. 'Chirality and Biological Activity', Eds. B. Holmstedt, H. Frank, B. Testa, Liss, New York, 1990, 283 p.
6. 'Problems and Wonders of Chiral Molecules', Ed. M. Simonyi, Akadémiai Kiadõ, Budapest, 1990, 400 p.
7. 'Stereoselectivity of Pesticides-Biological and Chemical Problems', Eds. E. J. Ariëns, J. J. S. van Rensen, W. Welling, Elsevier, Amsterdam, 1988, 544 p.
8. 'Stereochemistry and Biological Activity of Drugs', Eds. E. J. Ariëns, W. Soudijn, P. B. M. Timmermans, Blackwell, Oxford, 1983, 194 p.
9. 'Stereochemistry', Ed. C. Tamm, Elsevier, Amsterdam, 1982, 342 p.
10. G. H. Wagnière, 'On Chirality and the Universal Asymmetry', Verlag Helvetica Chimica Acta, Zürich, and Wiley-VCH, Weinheim, 2007, 247 p.
11. th Anniversary', Chirality 2008, 19, 89-98.
12. B. Testa, S. D. Krämer, 'The Biochemistry of Drug Metabolism-An Introduction-Part 1. Principles and Overview', Chem. Biodiversity 2006, 3, 1053-1101
13. B. Testa, S. D. Krämer, 'The Biochemistry of Drug Metabolism: Principles, Redox Reactions, Hydrolyses', Verlag Helvetica Chimica Acta, Zürich, and Wiley-VCH, Weinhein, 2008, Vol. 1, 319 p.
14. M. A. Piutti, 'Sur une nouvelle espèce d'asparagine', C. R. Hebd. Séances Acad. Sci. 1886, 134-138.
15. M. Gardner, 'The Ambidextrous Universe', Penguin Books, New York, 1982, 293 p.
16. A. R. Cushny, 'Biological Relations of Optically Isomeric Substances', Williams & Wilkins, Baltimore, 1926.
17. C. L. Dodgson [Lewis Carroll], 'Through the Looking-Glass and What Alice Found There', Macmillan, London, 1871 (in 'The Penguin Complete Lewis Carroll', Penguin Books, London, 1982).
18. J. M. Mayer, B. Testa, 'Chiral Recognition in Drug Metabolism and Disposition', Int. J. Bio-Chromatogr. 2000, 5, 297-312.
19. B. Testa, J. Mayer, 'Chiral Recognition in Biochemical Pharmacology: An Overview', in 'Stereochemical Aspects of Drug Action and Disposition', Eds. M. Eichelbaum, B. Testa, A. Somogyi, Springer Verlag, Berlin, 2003, pp. 143-159.
20. L. H. Easson, E. Stedman, 'Studies on the Relationship between Chemical Constitution and Physiological Action. V. Molecular Dissymmetry and Physiological Activity', Biochem. J. 1933, 27, 1257-1266.
21. A. R. Fersht, 'The Hydrogen Bond in Molecular Recognition', Trends Biochem. Sci. 1987, 12, 301-304.
22. V. R. Meyer, M. Rais, 'A Vivid Model of Chiral Recognition', Chirality 1989, 1, 167-169.
23. L. Salem, X. Chapuisat, G. Segal, P. C. Hiberty, C. Minot, C. Leforestier, P. Sautet, 'Chirality Forces', J. Am. Chem. Soc. 1987, 109, 2887-2894.
24. S. F. Mason, 'The Development of Concepts of Chiral Discrimination', Chirality 1989, 1, 183-191.
25. S. Topiol, M. Sabio, 'Elucidation of Chiral Recognition Principles', Enantiomer 1996, 1, 251-265.
26. T. D. Booth, D. Wahnon, I. W. Wainer, 'Is Chiral Recognition a Three-Point Process?', Chirality 1997, 9, 96-98.
27. V. A. Davankov, 'The Nature of Chiral Recognition: Is It a Three-Point Interaction', Chirality 1997, 9, 99-102.
28. R. Bentley, 'Diastereoisomerism, Contact Points, and Chiral Selectivity: a Four-Site Saga', Arch. Biochem. Biophys. 2003, 414, 1-12.
29. V. Sundaresan, R. Abrol, 'Biological Chiral Recognition: The Substate's Perspective', Chirality 2005, 17, S30-S39.
30. A. D. Mesecar, D. E. Koshland Jr., 'A New Model for Protein Stereospecificity', Nature 2000, 403, 614-615.
31. P. J. Rice, A. Hamada, D. D. Miller, P. N. Patil, 'Asymmetric Catecholimidazolines and Catecholamidines: Affinity and Efficacy Relationships at the alpha Adrenoceptor in Rat Aorta', J. Pharmacol. Exp. Ther. 1987, 242, 121-130
32. P. N. Patil, C. Li, V. Kumari, J. P. Hieble, 'Analysis of Efficacy of Chiral Adrenergic Agonists', Chirality 2008, 20, 529-543.
33. R. R. Ruffolo Jr., 'Chirality in α- and β-Adrenoceptor Agonists and Antagonists', Tetrahedron 1991, 48, 9953-9980.
34. P. Ciapetti, B. Ghiethlen, 'Molecular Variations Based on Isosteric Replacements', in 'The Practice of Medicinal Chemistry', 3rd edn., Ed. C. G. Wermuth, Academic Press, London, 2008, pp. 290- 342.
35. R. R. Ruffolo Jr., 'Important Concepts of Receptor Theory', J. Autonom. Pharmacol. 1982, 2, 277-295.
36. B. Testa, 'Mechanisms of Chiral Recognition in Xenobiotic Metabolism and Drug-Receptor Interactions', Chirality 1989, 1, 7-9.
37. B. Testa, 'Mechanisms of Chiral Recognition in Pharmacology: The Easson-Stedman Model Revisited', Acta Pharm. Nord. 1990, 2, 137-144.
38. R. R. Ruffolo Jr., T. A. Spradlin, G. D. Pollock, J. E. Waddell, P. J. Murphy, 'Alpha and Beta Adrenergic Effects of the Stereoisomers of Dobutamine', J. Pharmacol. Exp. Ther. 1981, 219, 447-452.
39. 1-Selective Adrenoceptor Agonist Dobutamine: A Fallacy Being Perpetuated', Chirality 2011, 23, 63-64.
40. 3H]Noradrenaline Release', Br. J. Pharmacol. 1985, 84, 477-487.
41. http://en.wikipedia.org/wiki/Hermann-Emil-Fischer.
42. D. E. Koshland Jr., 'Role of Flexibility in the Specificity, Control and Evolution of Enzymes', FEBS Lett. 1976, 62, E47-E52.
43. D. E. Koshland Jr., 'The Key-Lock Theory and the Induced Fit Theory', Angew. Chem., Int. Ed. 1994, 33, 2375-2378.
44. C. B. Post, W. J. Ray Jr., 'Reexamination of Induced Fit as a Determinant of Substrate Specificity in Enzymatic Reactions', Biochemistry 1995, 34, 15881-15885.
45. K. A. Johnson, 'Role of Induced Fit in Enzyme Specificity: A Molecular Forward/Reverse Switch', J. Biol. Chem. 2008, 283, 26297-26301.
46. C. A. Sotriffer, 'Accounting for Induced-Fit Effects in Docking: What Is Possible and What Is Not?', Curr. Top. Med. Chem. 2011, 11, 179-191.
47. J. P. Changeux, S. Edelstein, 'Conformational Selection or Induced Fit? 50 Years of Debate Resolved', F1000 Biol. Rep. 2011, 3, 19.
48. D. Herschland, 'The Role of Induced Fit and Conformational Changes of Enzymes in Specificity and Catalysis', Bioorg. Chem. 1988, 16, 62-96.
49. T. Kenakin, 'Receptor Conformational Induction versus Selection: All Part of the Same Energy Landscape', Trends Pharmacol. Sci. 1996, 17, 190-191
50. R. F. Bruns, 'Conformational Induction versus Conformational Selection: Evidence from Allosteric Enhancers', Trends Pharmacol. Sci. 1996, 17, 189.
51. G. G. Hammes, Y. C. Chang, T. G. Oas, 'Conformational Selection or Induced Fit: A Flux Description of Reaction Mechanism', Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 13737-13741.
52. D. D. Boehr, R. Nussinov, P. E. Wright, 'The Role of Dynamic Conformational Ensembles in Biomolecular Recognition', Nat. Chem. Biol. 2009, 5, 789-796.
53. T. R. Weikl, C. Deuster, 'Selected-Fit versus Induced-Fit Protein Binding: Kinetic Differences and Mutational Analysis', Proteins 2009, 75, 104-110.
54. P. Csermely, R. Palotai, R. Nussimov, 'Induced Fit, Conformational Selection and Independent Dynamic Segments: An Extended View of Binding Events', Trends Biochem. Sci. 2010, 35, 539-546.
55. H. X. Zhou, 'From Induced Fit to Conformational Selection: A Continuum of Binding Mechanism Controlled by the Timescale of Conformational Transitions', Biophys. J. 2010, 98, L15-L17.
56. D. A. Silva, G. R. Bowman, A. Sosa-Peinado, X. Huang, 'A Role for Both Conformational Selection and Induced Fit in Ligand Binding by the LAO Protein', PloS Comput. Biol. 2011, 7(5), e1002054.
57. H. X. Kondo, N. Okimoto, G. Morimoto, M. Taiji, 'Free Energy Landscapes of Protein Domain Movements upon Ligand Binding', J. Phys. Chem. B 2011, 115, 7629-7636.
58. G. Klebe, 'Mechanisms of Stereoselective Binding to Functional Proteins', in 'Stereochemical Aspects of Drug Action and Disposition', Eds. M. Eichelbaum, B. Testa, A. Somogyi, Springer Verlag, Berlin, 2003, pp. 183-198.
59. A. C. Kruse, J. Hu, A. C. Pan, D. H. Arlow, D. M. Rosenbaum, E. Rosemond, H. F. Green, T. Liu, P. S. Chae, R. O. Dror, D. E. Shaw, W. I. Weis, J. Wess, B. K. Kobilka, 'Structure and Dynamics of the M3 Muscarinic Acetylcholine Receptor', Nature 2012, 482, 552-556
60. K. Haga, A. C. Kruse, H. Asada, T. Yurugi-Kobayashi, M. Shiroishi, C. Zhang, W. I. Weis, T. Okada, B. K. Kobilka, T. Haga, T. Kobayashi, 'Structure of the Human M2 Muscarinic Acetylcholine Receptor Bound to an Antagonist', Nature 2012, 482, 547-551.
61. A. Pedretti, G. Vistoli, C. Marconi, B. Testa, 'Muscarinic Receptors: A Comparative Analysis of Structural Features and Binding Modes through Homology Modelling and Molecular Docking', Chem. Biodiversity 2006, 3, 481-501
62. A. Pedretti, G. Vistoli, B. Testa, R. Matucci, 'The Conformational and Property Space of Acetylcholine Bound to Muscarinic Receptors: An Entropy Component Accounts for the Subtype Selectivity of Acetylcholine', Arch. Biochem. Biophys. 2007, 464, 112-121.
63. G. Duncan, D. J. Collison, 'Role of the Non-Neuronal Cholinergic System in the Eye: A Review', Life Sci. 2003, 72, 2013-2019.
64. K. Cannard, 'The Acute Treatment of Nerve Agent Exposure', J. Neurol. Sci. 2006, 249, 86-94.
65. C. Ghelardini, F. Gualtieri, N. M. Romanelli, P. Angeli, G. Pepeu, G. M. Giovannini, F. Casamenti, P. Malmberg-Aiello, A. Giotti, A. Bartolini, 'Stereoselective Increase in Cholinergic Transmission by R-(+)-Hyoscyamine', Neuropharmacology 1997, 36, 281-294.
66. J. Singh, T. J. Hagen, 'Chirality and Biological Activity', in 'Burger's Medicinal Chemistry, Drug Discovery, and Development', 7th edn., Eds. D. J. Abraham, D. P. Rotella, John Wiley & Sons, Hoboken, 2010, pp. 127-166.
67. A. G. Draffan, G. R. Evans, J. A. Henshilwood, 'Chirality and Biological Activity', in 'Burger's Medicinal Chemistry & Drug Discovery, 6th edn., Ed. D. J. Abraham, John Wiley & Sons, Hoboken, 2003, pp. 781-826.
68. 'Chirality in Drug Design and Development', Eds. I. K. Reddy, R. Mehvar, Dekker, New York, 2004, 444 pages.
69. W. Soudijn, I. van Wijngaarden, A. P. Ijzerman, 'Stereoselectivity of Drug-Receptor Interactions', IDrugs 2003, 6, 43-56.
70. W. Soudijn, I. van Wijngaarden, A. P. Ijzerman, 'Enantioselectivity in Drug-Receptor Interactions', in 'Stereochemical Aspects of Drug Action and Disposition', Eds. M. Eichelbaum, B. Testa, A. Somogyi, Springer Verlag, Berlin, 2003, pp. 161-182.
71. C. Valenzuela, 'Stereoselective Drug-Channel Interactions', in 'Stereochemical Aspects of Drug Action and Disposition', Eds. M. Eichelbaum, B. Testa, A. Somogyi, Springer Verlag, Berlin, 2003, pp. 199-228.
72. D. J. Triggle, 'Stereoselectivity of Drug Action', Drug Discovery Today 1997, 2, 138-147
73. D. J. Triggle, 'The Stereoselectivity of Drug Action', Pharm. News 2001, 8, 10-13.
74. A. Brossi, 'Chiral Drugs: Synopsis', Med. Res. Rev. 1994, 14, 665-691.
75. B. Holmstedt, 'The Use of Enantiomers in Biological Studies: A Historical Review', in 'Chirality and Biological Activity', Eds. B. Holmstedt, H. Frank, B. Testa, Liss, New York, 1990, pp. 1-14.
76. M. Simonyi, 'On Chiral Drug Action', Med. Res. Rev. 1984, 4, 359-413.
77. P. S. Portoghese, 'Relationships between Stereostructure and Pharmacological Activities', Annu. Rev. Pharmacol. 1970, 10, 51-76.
78. A. H. Beckett, 'The Importance of Steric, Stereochemical and Physico-Organic Features in Drug Metabolism and Drug Action', Pure Appl. Chem. 1969, 19, 231-248.
79. A. H. Beckett, 'Stereochemical Factors in Biological Activity', in 'Progress in Drug Research. Vol. 1', Ed. E. Jucker, Birkhäuser, Basel, 1959, pp. 455-530.
80. C. D. Sieber, A. Hänsicke, T. Nagel, 'Stereochemical Comparison of Nebivolol with other β-Blockers', Chirality 2008, 20, 103-109.
81. K. E. Furse, T. P. Lybrand, 'Three-Dimensional Models for β-Adrenergic Receptor Complexes with Agonists and Antagonists', J. Med. Chem. 2003, 46, 4450-4462.
82. B. Waldeck, 'Chiral Aspects of β-Adrenergic Agonists', Pharm. News 2001, 8, 25-31.
83. 2-Adrenoceptors', J. Pharm. Pharmacol. 1988, 40, 609-612.
84. R. T. Coutts, G. B. Baker, 'Implications of Chirality and Geometic Isomerism in Some Psychoactive Drugs and Their Metabolites', Chirality 1989, 1, 99-120.
85. D. J. Triggle, 'Ion Channels as Pharmacologic Receptors: The Chirality of Drug Interactions', Chirality 1996, 8, 35-38
86. D. J. Triggle, 'On the Other Hand: The Stereoselectivity of Drug Action at Ion Channels', Chirality 1994, 6, 58-62.
87. S. Goldmann, J. Stoltefuss, '1,4-Dihydropyridines-Effects of Chirality and Conformation on the Calcium Antagonists and Calcium Agonist Activities', Angew. Chem., Int. Ed. 1991, 30, 1559-1578.
88. E. J. Moody, 'Chirality and General Anesthetic Action', Pharm. News 2001, 8, 36-41.
89. N. P. Franks, W. R. Lieb, 'Molecular and Cellular Mechanisms of General Anaesthesia', Nature 1994, 367, 607-614.
90. J. Caldwell, B. Testa, 'Criteria for the Acceptability of Experimental Evidence for the Enantiomeric Composition of Xenobiotics and Their Metabolites', Drug Metab. Dispos. 1987, 15, 587-588.
91. R. B. Barlow, F. M. Franks, J. D. M. Pearson, 'The relation between biological activity and the degree of optical resolution of optical isomers', J. Pharm. Pharmacol. 1972, 24, 753-761.
92. J. Trofast, K. Österberg, B. L. Källström, B. Waldeck, 'Steric Aspects of Agonism and Antagonism at β-Adrenoceptors: Synthesis of and Pharmacological Experiments with the Enantiomers of Formoterol and Their Diastereomers', Chirality 1991, 3, 443-450.
93. B. Waldeck, 'Biological Significance of the Enantiomeric Purity of Drugs', Chirality 1993, 5, 350-355.
94. C. C. Pfeiffer, 'Optical Isomerism and Pharmacological Action, a Generalization', Science 1956, 124, 29-31.
95. R. Barlow, 'Enantiomers: How Valid is Pfeiffer's Rule?', Trends Pharmacol. Sci. 1990, 11, 148-150.
96. E. J. Ariëns, A. M. Simonis, 'Cholinergic and Anticholinergic Drugs, Do They Act on Common Receptors?', Ann. N.Y. Acad. Sci. 1967, 144, 842-868.
97. P. A. F. Lehmann, J. F. Rodrigues de Miranda, E. J. Ariëns, 'Stereoselectivity and Affinity in Molecular Pharmacology', in 'Progress in Drug Research', Ed. E. Jucker, Birkhäuser, Basel, 1976, Vol. 20, pp. 101-129.
98. P. A. F. Lehmann, 'Quantifying Stereoselectivity or How to Choose a Pair of Shoes when You Have Two Left Feet', Trends Pharmacol. Sci. 1982, 3, 103-106
99. P. A. F. Lehmann, 'Stereoisomerism and Drug Action', Trends Pharmacol. Sci. 1986, 7, 281-285.
100. P. A. F. Lehmann, 'A Quantitative Stereo-Structure Activity Relationship Analysis of the Binding of Promiscuous Chiral Ligands to Different Receptors', Quant. Struct.-Act. Relat. 1987, 6, 57-65.
101. H. van de Waterbeemd, N. El Tayar, B. Testa, H. Wikström, B. Largent, 'Quantitative Structure-Activity Relationships and Eudismic Analyses of the Presynaptic Dopaminergic Activity and Dopamine D2 and Sigma Receptor Affinities of 3-(3-Hydroxyphenyl)-piperidines and Octahydrobenzo[f]quinolines', J. Med. Chem. 1987, 30, 2175-2181.
102. K. J. Romstedt, L. P. Lei, D. R. Feller, D. T. Witiak, F. Loiodice, V. Tortorella, 'Differential Eudismic Ratios in the Antagonism of Human Platelet Function by Phenoxy- and Thiophenoxyacetic Acids', Farmaco 1996, 51, 107-114.
103. K. Ding, J. Chen, M. Jin, X. Wu, J. Varady, C. Y. Yang, Y. Lu, J. R. Deschamps, B. Levant, S. Wang, 'Enantiomerically Pure Hexahydropyrazinoquinolines as Potent and Selective Dopamine 3 Subtype Receptor Ligands', J. Med. Chem. 2005, 48, 3171-3181.
104. 1-Receptor Antagonists', Biochem. Pharmacol. 2003, 66, 1123-1126.
105. 194', Mol. Pharmacol. 2002, 61, 391-399.
106. A. D. Hughes, S. Hering, T. B. Bolton, 'Evidence That Agonist and Antagonist Enantiomers of the Dihydropyridine PN 202-791 Act at Different Sites on the Voltage-Dependent Calcium Channel of Vascular Muscle', Br. J. Pharmacol. 1990, 101, 3-5.
107. D. Conte Camerino, M. Mambrini, A. De Luca, D. Tricarico, S. H. Bryant, V. Tortorella, G. Bettoni, 'Enantiomers of Clofibric Acid Analogs Have Opposite Actions on Rat Skeletal Muscle Chloride Channels', Eur. J. Physiol. 1988, 413, 105-107.
108. A. De Luca, D. Tricarico, R. Wagner, S. H. Bryant, V. Tortorella, D. Conte Camerino, 'Opposite Effects of Enantiomers of Clofibric Acid Derivative on Rat Skeletal Muscle Chloride Conductance: Antagonism Studies and Theoretical Modeling of Two Different Receptor Site Interactions', J. Pharmacol. Exp. Ther. 1992, 260, 364-368.
109. B. Jiang, H. Wang, Q. M. Fu, Z. Y. Li, 'The Chiral Pyrethroid Cycloprothin: Stereoisomer Synthesis and Separation and Stereoselective Insecticidal Activity', Chirality 2008, 20, 96-102.
110. C. B. Eap, S. Crettol, J. S. Rougier, J. Schläpfer, L. Sintra Grilo, J. J. Déglon, J. Besson, M. Croquette-Krokar, P. A. Carrupt, H. Abriel, 'Stereoselective Block of hERG Channel by (S)-Methadone and QT Interval Prolongation in CYP2B6 Slow Metabolizers', Clin. Pharmacol. Ther. 2007, 81, 719-728.
111. H. Abriel, J. Schläpfer, D. I. Keller, B. Gavillet, T. Buclin, J. Biollaz, R. Stoller, L. Kappenberger, 'Molecular and Clinical Determinants of Drug-Induced Long QT Syndrome: A Iatrogenic Channelopathy', Swiss Med. Weekly 2004, 134, 685-694.
112. A. M. Aronov, 'In silico Models to Predict QT Prolongation', in 'ADME-Tox Approaches', B. Testa, H. van de Waterbeemd, Eds., Vol. 5 in 'Comprehensive Medicinal Chemistry', 2nd edn, Eds. J. B. Taylor, D. J. Triggle, Elsevier, Oxford, 2007, pp. 933-954.
113. N. Ansermot, O. Albayrak, J. Schläpfer, S. Crettol, M. Croquette-Krokar, M. Bourquin, J. J. Déglon, M. Faouzi, N. Scherbaum, C. B. Eap, 'Substitution of (R,S)-Methadone by (R)-Methadone', Arch. Internal Med. 2010, 170, 529-536.
114. I. N. Pessah, H. J. Lehmler, L. W. Robertson, C. F. Perez, E. Cabrales, D. D. Bose, W. Feng, 'Enantiomeric Specificity of (-)-2,2′,3,3′,6, 6′-Hexachlorobiphenyl toward Ryanodine Receptor Types 1 and 2', Chem. Res. Toxicol. 2008, 22, 201-207.
115. R. A. Palmer, B. S. Potter, M. J. Leach, T. C. Jenkins, B. Z. Chowdhry, 'An Absolute Structure Template for a Unique Voltage-Gated Sodium Channel Binding Site', Med. Chem. Commun. 2010, 1, 45-49.
116. V. M. Vrudhula, B. Dasgupta, J. Qian-Cutrone, E. S. Kozlowski, C. G. Boissard, S. I. Dworetzky, D. Wu, Q. Gao, R. Kimura, V. K. Gribkoff, J. E. Starrett Jr., 'Atropisomeric 3-(β-hydroxyethyl)-4-arylquinolin-2-ones as Maxi-K Potassium Channel Openers', J. Med Chem. 2007, 50, 1050-1057.
117. Y. S. Zhou, L. K. Tay, D. Hughes, S. Donahue, 'Simulation of the Impact of Atropisomer Interconversion on Plasma Exposure of Atropisomers of an Endothelin Receptor Antagonist', J. Clin. Pharmacol. 2004, 44, 680-688.
118. B. Testa, S. D. Krämer, 'The Biochemistry of Drug Metabolism-An Introduction. Part 5: Metabolism and Bioactivity', Chem. Biodiversity 2009, 6, 591-684
119. B. Testa, S. D. Krämer, 'The Biochemistry of Drug Metabolism: Conjugations, Consequences of Metabolism, Influencing Factors', Verlag Helvetica Chimica Acta, Zürich, and Wiley-VCH, Weinhein, 2010, 588 p.
120. T. J. Edkins, M. Fronheiser, D. R. Bobbitt, J. E. Mills, T. M. Rossi, 'Enantiomeric Quantitation without Separation of Tramadol via Laser-Based Polarimetry', Enantiomer 1996, 1, 97-107.
121. R. B. Raffa, E. Friderichs, W. Reimann, R. P. Shank, E. E. Codd, J. L. Vaught, H. I. Jacoby, N. Selve, 'Complementary and Synergistic Antinociceptive Interaction between the Enantiomers of Tramadol', J. Pharmacol. Exp. Ther. 1993, 267, 331-340.
122. L. J. Scott, C. M. Perry, 'Tramadol. A Review of Its Use in Perioperative Pain', Drugs 2000, 60, 139-176.
123. M. Valle, M. J. Garrido, J. M. Pavõn, R. Calvo, I. F. Trocõniz, 'Pharmacokinetic-Pharmacodynamic Modeling of the Antinocipeptive Effects of Main Active Metabolites of Tramadol, (+)-O-Desmethyltramadol and (-)-Desmethyltramadol, in Rats', J. Pharmacol. Exp. Ther. 2000, 293, 646-653.
124. S. Grond, T. Meuser, H. Uragg, H. J. Stahlberg, K. A. Lehmann, 'Serum Concentrations of Tramadol Enantiomers during Patient-Controlled Analgesia', Br. J. Clin. Pharmacol. 1999, 48, 254-257.
125. J. M. Mayer, B. Testa, 'Pharmacodynamics, Pharmacokinetics and Toxicity of Ibuprofen Enantiomers', Drugs Future 1997, 22, 1347-1366.
126. I. Tegeder, K. Williams, G. Geisslinger, 'Metabolic Chiral Inversion of 2-Arylpropionic Acids', in 'Stereochemical Aspects of Drug Action and Disposition', Eds. M. Eichelbaum, B. Testa, A. Somogyi, Springer Verlag, Berlin, 2003, pp. 341-354.
127. J. M. Mayer, M. Roy-de Vos, C. Audergon, B. Testa, 'Interactions between the in vitro Metabolism of Xenobiotics and Fatty Acids. The Case of Ibuprofen and Other Chiral Profens', Arch. Toxicol. 1995, Suppl. 17, 499-513.
128. H. Hao, G. Wang, J. Sun, 'Enantioselective Pharmacokinetics of Ibuprofen and Involved Mechanisms', Drug Metab. Rev. 2005, 37, 215-234.
129. K. M. Knights, C. J. Drogemuller, 'Xenobiotic-CoA Ligases: Kinetic and Molecular Characterization', Curr. Drug Metab. 2000, 1, 49-66
130. K. M. Knights, 'Role of Hepatic Fatty Acid:Coenzyme A Ligases in the Metabolism of Xenobiotic Carboxylic Acids', Clin. Exp. Pharmacol. Physiol. 1998, 25, 776-782.
131. R. Brugger, C. Reichel, B. Garcia Alia, K. Brune, T. Yamamoto, I. Tegeder, G. Geisslinger, 'Expression of Rat Liver Long-Chain Acyl-CoA Synthetase and Characterization of Its Role in the Metabolism of R-Ibuprofen and other Fatty Acid-Like Xenobiotics', Biochem. Pharmacol. 2001, 61, 651-656.
132. M. D. Lloyd, D. J. Darley, A. S. Wierzbicki, M. D. Threadgill, 'Alpha-Methylacyl-CoA Racemase-an 'Obscure' Metabolic Enzyme Takes Centre Stage', FEBS J. 2008, 275, 1089-1102.
133. W. Neupert, R. Brugger, C. Euchenhofer, K. Brune, G. Geisslinger, 'Effects of Ibuprofen Enantiomers and Its Coenzyme A Thioesters on Human Prostaglandin Endoperoxide Synthases', Br. J. Pharmacol. 1997, 122, 487-492.
134. N. Levoin, C. Blondeau, C. Guillaume, L. Grandcolas, F. Chrétien, J.-Y. Jouzeau, E. Benoit, Y. Chapleur, P. Netter, F. Lapicque, 'Elucidation of the Mechanism of Inhibition of Cyclooxygenases by Acyl-CoA and Acyl Glucuronide Conjugates of Ketoprofen', Biochem. Pharmacol. 2004, 68, 1957-1969.
135. 'Drug Bioavailability-Estimation of Solubility, Permeability, Absorption and Bioavailability', 2nd edn., Eds. H. van de Waterbeemd, B. Testa, Wiley-VCH, Weinheim, 2008, 624 p.
136. 'ADME-Tox Approaches', Eds. B. Testa, H. van de Waterbeemd, Vol. 5 in 'Comprehensive Medicinal Chemistry', 2nd edn., Eds. J. B. Taylor, D. J. Triggle, Elsevier, Oxford, 2007.
137. H. van de Waterbeemd, B. Testa, 'The Why and How of Absorption, Distribution, Metabolism, Excretion and Toxicity Research', in 'ADME-Tox Approaches', Eds. B. Testa, H. van de Waterbeemd, Vol. 5 in 'Comprehensive Medicinal Chemistry', 2nd edn., Eds. J. B. Taylor, D. J. Triggle, Elsevier, Oxford, 2007, pp. 1-9.
138. D. R. Brocks, 'Drug Disposition in Three Dimensions: An Update on Stereoselectivity in Pharmacokinetics', Biopharm. Drug Dispos. 2006, 27, 387-406.
139. G. T. Tucker, M. S. Lennard, 'Enantiomer Specific Pharmacokinetics', Pharmacol. Ther. 1990, 45, 309-329.
140. R. Mehvar, D. R. Brocks, M. Vakily, 'Impact of Stereoselectivity on the Pharmacokinetics and Pharmacodynamics of Antiarrhythmic Drugs', Clin. Pharmacokinet. 2002, 41, 533-558.
141. R. R. Shah, 'Improving Clinical Risk/Benefit through Stereochemistry', in 'Stereochemical Aspects of Drug Action and Disposition', Eds. M. Eichelbaum, B. Testa, A. Somogyi, Springer Verlag, Berlin, 2003, pp. 401-432.
142. K. Arimori, K. Yasuda, H. Katsuki, M. Nakano, 'Pharmacokinetic Differences between Lansoprazole Enantiomers in Rats', J. Pharm. Pharmacol. 1998, 50, 1241-1245.
143. P. M. Cerqueira, E. J. Cesarino, F. H. Mateus, Y. Mere Jr., S. R. Cavani, V. L. Lanchote, 'Enantioslectivity in the Steady-State Pharmacokinetics of Metoprolol in Hypertensive Patients', Chirality 1999, 11, 591-597.
144. J. Guan, J. Yang, J. Li, F. Li, 'Determination of Tenatoprazole Enantiomers and Their Enantioselective Pharmacokinetics in Rats', Chirality 2009, 21, 613-618.
145. A. L. Pardo, C. Godoy, C. C. Parisi, M. P. Marques, E. B. Coelho, V. L. Lanchote, 'Enantioselective Determination of Mexiletine and Its Metabolites p-Hydroxymexiletine and Hydroxymethylmexiletine in Rat Plasma by Normal-Phase LC-Tandem MS: Application to Pharmacokinetics', Chirality 2009, 21, 648-656.
146. M. Miura, T. Uno, M. Takeishi, T. Suzuki, 'Pharmacokinetics of Fexofenadine Enantiomers in Healthy Subjects', Chirality 2007, 19, 223-227.
147. Y. Akamine, M. Miura, S. Sunagawa, H. Kagaya, N. Yasui-Furukori, T. Uno, 'Influence of Drug-Transporter Polymorphisms on the Pharmacokinetics of Fexofenadine Enantiomers', Xenobiotica 2010, 40, 782-789.
148. U. Fagerholm, 'The Role of Permeability in Drug ADME/PK, Interactions and Toxicity, and the Permeability-Based Classification Systems (PCS)', in 'Burger's Medicinal Chemistry, Drug Discovery, and Development', 7th edn., Eds. D. J. Abraham, D. P. Rotella, John Wiley & Sons, Hoboken, 2010, pp. 367-379.
149. P. Artursson, S. Neuhoff, P. Matsson, S. Tavelin, 'Passive Permeability and Active Transport Models for the Prediction of Oral Absorption', in 'ADME-Tox Approaches', Eds. B. Testa, H. van de Waterbeemd, Vol. 5 in 'Comprehensive Medicinal Chemistry', 2nd edn., Eds. J. B. Taylor, D. J. Triggle, Elsevier, Oxford, 2007, pp. 259-278.
150. C. M. Head, K. R. Brain, 'Does Solute Stereochemistry Influence Percutaneous Penetration?', Chirality 1995, 7, 305-309.
151. W. Jäger, M. Mayer, G. Reznicek, G. Buchbauer, 'Percutaneous Absorption of the Monoterpene Carvone: Implication of Stereoselective Metabolism on Blood Levels', J. Pharm. Pharmacol. 2001, 53, 637-642.
152. A. Pagliara, P. A. Carrupt, G. Caron, P. Gaillard, B. Testa, 'Lipophilicity Profiles of Ampholytes', Chem. Rev. 1997, 97, 3385-3400.
153. R. S. Tsai, P. A. Carrupt, B. Testa, N. El Tayar, G. L. Grunewald, A. F. Casy, 'Influence of Stereochemical Factors on the Partition Coefficient of Diastereomers in a Biphasic Octan-1-ol/Water System', J. Chem. Res. (S) 1993, 298-299, J. Chem. Res. (M) 1993, 1901-1920.
154. J. M. Scherrmann, 'The Biology and Function of Transporters', in 'ADME-Tox Approaches', Eds. B. Testa, H. van de Waterbeemd, Vol. 5 in 'Comprehensive Medicinal Chemistry', 2nd edn., Eds. J. B. Taylor, D. J. Triggle, Elsevier, Oxford, 2007, pp. 51-85.
155. P. Anderle, C. U. Nielsen, 'Transporters in the Gastrointestinal Tract', in 'Drug Bioavailability-Estimation of Solubility, Permeability, Absorption and Bioavailability', 2nd edn., Eds. H. van de Waterbeemd, B. Testa, Wiley-VCH, Weinheim, 2008, pp. 223-276
156. H. Spahn-Langguth, C. Dressler, C. Leisen, 'Intestinal Drug Transport: Stereochemical Aspects', in 'Stereochemical Aspects of Drug Action and Disposition', Eds. M. Eichelbaum, B. Testa, A. Somogyi, Springer Verlag, Berlin, 2003, pp. 251-288.
157. K. Maeda, H. Suzuki, Y. Sugiyama, 'Hepatic Transport', in 'Drug Bioavailability-Estimation of Solubility, Permeability, Absorption and Bioavailability', 2nd edn., Eds. H. van de Waterbeemd, B. Testa, Wiley-VCH, Weinheim, 2008, pp. 277-332.
158. K. M. Giacomini, S.-M. Huang, D. J. Tweedie, and, The International Transporter Consortium, 'Membrane Transporters in Drug Development', Nat. Rev. Drug Discovery 2010, 9, 215-236.
159. S. G. Aller, J. Yu, A. Ward, Y. Weng, S. Chittaboina, R. Zhuo, P. M. Harrell, Y. T. Trinh, Q. Zhang, I. L. Urbatsch, G. Chang, 'Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding', Science 2009, 323, 1718-1722.
160. F. Stoll, A. H. Göller, A. Hillisch, 'Utility of Protein Structures in Overcoming ADMET-Related Issues of Drug-Like Compounds', Drug Discovery Today 2011, 16, 530-538.
161. J.-P. Becker, G. Depret, F. Van Bambeke, P. M. Tulkens, M. Prévost, 'Molecular Models of Human P-Glycoprotein in Two Different Catalytic States', BMC Struct. Biol. 2009, doi:10.1186/1472-6807-9-3.
162. E. Dolghih, C. Bryant, A. R. Renslo, M. P. Jacobson, 'Predicting Binding to P-Glycoprotein by Flexible Receptor Docking', PLoS Comput. Biol. 2011, 7(6), e1002083.
163. C. M. Brett, R. J. Orr, K. M. Giacomini, 'Stereoselective Renal Elimination', in 'Stereochemical Aspects of Drug Action and Disposition', Eds. M. Eichelbaum, B. Testa, A. Somogyi, Springer Verlag, Berlin, 2003, pp. 355-375.
164. E. Choong, M. Dobrinas, P. A. Carrupt, C. B. Eap, 'The Permeability P-Glycoprotein: A Focus on Enantioselectivity and Brain Distribution', Exp. Opin. Drug Metab. Toxicol. 2010, 6, 953-965.
165. A. G. Leach, E. A. Pilling, A. A. Rabow, S. Tomasi, N. Asaad, N. J. Buurma, A. Ballard, S. Narduolo, 'Enantiomeric Pairs Reveal that Key Medicinal Chemistry Parameters vary more than Simple Physical Property Based Models Can Explain', Med. Chem. Commun. 2012, 3, 528-540.
166. S. Crettol, P. Digon, K. Powell Golay, M. Brawand, C. B. Eap, 'In vitro P-Glycoprotein-Mediated Transport of (R)-, (S)-, (R,S)-Methadone, LAAM and Their Main Metabolites', Pharmacology 2007, 80, 304-311.
167. S. Baudry, Y. T. Pham, B. Baune, S. Vidrequin, C. Crevoisier, F. Gimenez, R. Farinotti, 'Stereoselective Passage of Mefloquine through the Blood-Brain Barrier in the Rat', J. Pharm. Pharmacol. 1997, 49, 1086-1090.
168. Y. Gu, G. J. Wang, X. L. Wu, Y. T. Zheng, J. W. Zhang, H. Ai, J. G. Sun, Y. W. Jia, 'Intestinal Absorption Mechanisms of Ginsenoside Rh2: Stereoselectivity and Involvement of ABC Transporters', Xenobiotica 2010, 40, 602-612.
169. J. Zhang, F. Zhou, F. Niu, M. Lu, X. Wu, J. Sun, G. Wang, 'Stereoselective Regulations of P-Glycoprotein by Ginsenoside Rh2 Epimers and the Potential Mechanisms from the View of Pharmacokinetics', PLoS One 2012, 7(4), e35768.
170. P. Barton, R. P. Austin, R. E. Fessey, 'In vitro Models for Plasma Binding and Tissue Storage', in 'ADME-Tox Approaches', Eds. B. Testa, H. van de Waterbeemd, Vol. 5 in 'Comprehensive Medicinal Chemistry', 2nd edn., Eds. J. B. Taylor, D. J. Triggle, Elsevier, Oxford, 2007, pp. 321-340.
171. J. P. Tillement, G. Houin, R. Zini, S. Urien, E. Albengres, J. Barré, M. Lecomte, P. D'Athis, B. Sébille, 'The Binding of Drug to Blood Plasma Macromolecules: Recent Advances and Therapeutic Significance', in 'Advances in Drug Research', Ed. B. Testa, Academic Press, London, 1984, Vol. 13, pp. 59-94.
172. B. Fichtl, A. von Nieciecki, K. Walter, 'Tissue Binding versus Plasma Binding of Drugs: General Principles and Pharmacokinetic Consequences', in 'Advances in Drug Research. Vol. 20', Ed. B. Testa, Academic Press, London, 1991, pp. 117-166.
173. A. Varshney, P. Sen, E. Ahmad, M. Rehan, N. Subbarao, R. H. Khan, 'Ligand Binding Strategies of Human Serum Albumin: How Can the Cargo Be Utilized?', Chirality 2010, 22, 77-87.
174. F. Hervé, G. Caron, J. C. Duché, P. Gaillard, N. Abd. Rahman, A. Tsantili-Kakoulidou, P. A. Carrupt, P. d'Athis, J. P. Tillement, B. Testa, 'Ligand Specificity of the Genetic Variants of Human alpha-1-Acid Glycoprotein. Generation of a 3D-QSAR Model for Drug Binding to the A Variant', Mol. Pharmacol. 1998, 54, 129-138.
175. L. Escuder-Gilabert, M. A. Martínez-Gõmez, R. M. Villanueva-Camañas, S. Sagrado, M. J. Medina-Hernández, 'Microseparation Techniques for the Study of the Enantioselectivity of Drug-Plasma Protein Binding', Biomed. Chromatogr. 2009, 23, 225-238.
176. P. J. Hayball, D. Mauleõn, 'Enantioselective Plasma and Tissue Binding', in 'Stereochemical Aspects of Drug Action and Disposition', Eds. M. Eichelbaum, B. Testa, A. Somogyi, Springer Verlag, Berlin, 2003, pp. 289-311.
177. Y. Hong, Y. Tang, S. Zeng, 'Enantioselective Plasma Protein Binding of Propafenone: Mechanism, Drug Interaction, and Species Differences', Chirality 2009, 21, 692-698.
178. T. Rodgers, D. Leahy, M. Rowland, 'Tissue Distribution of Basic Drugs: Accounting for Enantiomeric, Compound and Regional Differences among β-Blocking Drugs in Rat', J. Pharm. Sci. 2005, 94, 1237-1248.
179. R. Pérez-Ruiz, R. Alonso, E. Nuin, I. Andreu, M. C. Jiménez, M. A. Miranda, 'Naphthalene Triplet Excited State as a Probe for the Assessment of Drug Distribution in Binary Protein Systems', J. Phys. Chem. B 2011, 115, 4460-4468
180. Y. Ding, X. Zhu, B. Lin, 'Study of Interaction between Drug Enantiomers
181. G. Sager, R. Jaeger, C. Little, 'Binding of Prazosin and Propranolol at Variable alpha 1-Acid Glycoprotein and Albumin Concentrations', Br. J. Clin. Pharmacol. 1989, 27, 229-234.
182. M. Kurono, A. Fujii, M. Murata, B. Fujitani, T. Negoro, 'Stereospecific Recognition of a Spirosuccinimide Type Aldose Reductase Inhibitor (AS-3201) by Plasma Proteins: A Significant Role of Specific Binding by Serum Albumin in the Improved Potency and Stability', Biochem. Pharmacol. 2006, 71, 338-353.