Organic Stereochemistry. Part 51. Issue 5 (17th May 2013)

• Record Type: Journal Article
• Authors: Testa, Bernard; Vistoli, Giulio; Pedretti, Alessandro; Caldwell, John
• Is Part Of: Helvetica chimica acta. Volume 96:Issue 5(2013:May)
• Page Start: 747
• Page End: 798
• Publication Date: 2013-05-17
• Subjects: Chemistry -- Periodicals; Chemistry, Analytical -- periodicals; Chimie -- Périodiques; 540
• DOI: 10.1002/hlca.201200473
• Languages: English
• ISSNs: 0018-019X

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>This review continues a general presentation of the principles of stereochemistry with special reference to the medicinal sciences. Here, we discuss and illustrate molecular and clinical phenomena of stereoselectivity in pharmacological effects, namely activity differences between stereoisomers, principally enantiomers. The review begins with didactic models of chiral recognition, with a main focus on the early model of <italic>Easson</italic> and <italic>Stedman.</italic> There follows a Molecular Modeling (MM) and Molecular Dynamics (MD) depiction of the differential interaction of the enantiomers of hyoscyamine with cholinergic muscarinic receptors. The next section is devoted to various rationalizations in stereoselective pharmacological activity, <italic>e.g.</italic>, the influence of optical purity on enantioselectivity, <italic>Pfeiffer</italic>'s rule, and eudismic analysis. The review ends with selected examples taken from various fields of preclinical and clinical pharmacology, of differences between stereoisomers in terms of drug absorption, distribution, and excretion. The influence of conformational factor in molecular pharmacology will be discussed in <italic>Part 6</italic>, while stereoselective aspects of xenobiotic metabolism will be reviewed in <italic>Parts 7</italic> and <italic>8.</italic></p> </abstract>