Chiral drugs

Chemical compounds that come as mirror-image pairs are referred to by chemists as chiral or handed molecules.[1] Each twin is called an enantiomer. Drugs that exhibit handedness are referred to as chiral drugs. Chiral drugs that are equimolar (1:1) mixture of enantiomers are called racemic drugs and these are obviously devoid of optical rotation. The most commonly encountered stereogenic unit,[2] that confers chirality to drug molecules are stereogenic center. Stereogenic center can be due to the presence of tetrahedral tetra coordinate atoms (C,N,P) and pyramidal tricoordinate atoms (N,S). The word chiral describes the three-dimensional architecture of the molecule and does not reveal the stereochemical composition. Hence "chiral drug" does not say whether the drug is racemic (racemic drug), single enantiomer (chiral specific drug) or some other combination of stereoisomers. To resolve this issue Joseph Gal introduced a new term called unichiral.[3][4] Unichiral indicates that the stereochemical composition of a chiral drug is homogenous consisting of a single enantiomer.

Many medicinal agents important to life are combinations of mirror-image twins. Despite the close resemblance of such twins, the differences in their biological properties can be profound. In other words, the component enantiomers of a racemic chiral drug may differ wildly in their pharmacokinetic, pharmacodynamic profile.[5][6][7][8] The tragedy of thalidomide illustrates the potential for extreme consequences resulting from the administration of a racemate drug that exhibits multiple effects attributable to individual enantiomers.[9] With the advancements in chiral technology and the increased awareness about three-dimensional consequences of drug action and disposition emerged specialized field "chiral pharmacology". Simultaneously the chirality nomenclature system also evolved. A brief overview of chirality history and terminology/descriptors is given below. A detailed chirality timeline is not the focus of this article.

  1. ^ Bassindale, A (1984). The Third Dimension in Organic Chemistry. New York: John Wiley, New York. ISBN 047190189X.
  2. ^ Mislow, Kurt; Siegel, Jay (1984). "Stereoisomerism and local chirality". Journal of the American Chemical Society. 106 (11): 3319–3328. doi:10.1021/ja00323a043. ISSN 0002-7863.
  3. ^ Gal, Joseph; Lindner, wolfgang (2006). "Chiral drugs from a historical point of view". In Francotte, Eric (ed.). Chirality in drug research. Germany: Wiley-VCH Verlag GmbH & Co. pp. 3–26. ISBN 3-527-31076-2.
  4. ^ Gal, J (1998). "Problems of stereochemical nomenclature and terminology. 1. The homochiral controversy. Its nature, origins, and a proposed solution". Enantiomer. 3: 263–273.
  5. ^ Jamali, F.; Mehvar, R.; Pasutto, F.M. (1989). "Enantioselective Aspects of Drug Action and Disposition: Therapeutic Pitfalls". Journal of Pharmaceutical Sciences. 78 (9): 695–715. doi:10.1002/jps.2600780902. ISSN 0022-3549. PMID 2685226.
  6. ^ Williams, Kenneth M. (1991), Molecular Asymmetry and Its Pharmacological Consequences, Advances in Pharmacology, vol. 22, Elsevier, pp. 57–135, doi:10.1016/s1054-3589(08)60033-2, ISBN 978-0-12-032922-9, PMID 1958505, retrieved 2021-06-03
  7. ^ Crossley, Roger (1992). "The relevance of chirality to the study of biological activity". Tetrahedron. 48 (38): 8155–8178. doi:10.1016/s0040-4020(01)80486-5. ISSN 0040-4020.
  8. ^ Gross, Michael (1990), Chapter 34. Significance of Drug Stereochemistry in Modern Pharmaceutical Research and Development, Annual Reports in Medicinal Chemistry, vol. 25, Elsevier, pp. 323–331, doi:10.1016/s0065-7743(08)61610-3, ISBN 978-0-12-040525-1, retrieved 2021-06-03
  9. ^ Decamp, W (1989). "The FDA perspective on the development of stereoisomers". Chirality. 1 (1): 2–6. doi:10.1002/chir.530010103. PMID 2642032.