Chirality in drug discovery research
Uli Hacksell · Acta Crystallographica Section A Foundations of Crystallography · 1996
Regulatory requirements regarding documentation of chiral drugs have been increased during recent years.Today, a new drug application of a chiral drug normally contains pharmacodynamic, pha1111acokinetic and toxicological documentation on the individual enantiomers even if it is the racemate that is considered for therapeutic use.This additional documentation is time consuming and increases the cost for drug development.It might, therefore, be advantageous to aim for the development of achiral dmgs.However, in drug discovery resemch, chiral drugs may offer certain advantages; provided that enantiopure compounds me studied, chiral molecules will provide much more information about receptor/enzyme -ligand/substrate interactions than achiral analogues.In addition, recently developed synthetic methods affording enantiopure compounds and analytical methods for quantifying enantiopurity are available.Several examples will be given demonstrating that enantiopure ligands have provided essential information on the moleculm basis for activation of G-protein coupled receptors.It is of pa1ticulm interest that the chirality of a receptor ligand may be used to fine-tune the pham1acological profile.