Chemical Abstracts Stereochemical Nomenclature of Organic Substances in the Ninth Collective Period (1972-1976)

Stereoselectivity in clinical pharmacokinetics and drug development

“…such that the prefixes of (+) and (-) are synonymous with (d) and (l) to denote optical rotation but not with (D) and (L) or (R) and (5), which provide descriptors of absolute configuration, Although guidelines have been laid down in IUPAC rules and monographs (12) and in the Cahn, Ingold and Prelog (13) convention suggesting that both the absolute descriptors, R or S, should be placed before the rotational optical descriptor in parenthesis (+) or (-), the instructions to contributors in the journal Chirality ask for the reverse whilst in the Chemical Abstract Rules (14) the optical descriptors are omitted. Further complications arise with isomerism at double bonds, diastereomers; with interchangeable Z or E or cis or trans descriptors, where there may not be a 50150 mixture, where both diastereomer and enantiomers co-exist in the same molecule, when a crystallised salt, e.g.…”

“…If separation or specific chiral synthesis is not possible or on a large scale economically prohibitive then racemate development will follow [2] with all its difficulties hut small scale separation [3] will allow preclinical testing of both enantiomers. Conditions which strongly suggest the development of a single preferred enantiomer, (+), are (a) feasible large scale production [4]; (b) dister inverts to eutomer IU solution [5]; (c) the activity of the eutomer is very much greater than the distimer [6]; (d) the distimer interacts with the eutomer or other drugs in pharmacology, toxicology or kinetics [7,9,12]; (e) the inactive distimer has equal or greater toxicity to the eutomer [8]; (f) plasma levels of a toxic distimer are greater than the eutomer [10]; (g) enantiomers are equi-activity but levels of the eutomer are very much greater [11]; (h) the distimer with some toxicity undergoes polymorphic metabolism [13] or produces toxic metabolites [14]; (i) clinical confmnation of activity with only one enantiomer [15].…”

“…Note that despite large differences in the enantiomeric ratio(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), the CL(RS)…”