Enantiomeric pairs reveal that key medicinal chemistry parameters vary more than simple physical property based models can explain

QSAR with experimental and predictive distributions: an information theoretic approach for assessing model quality

“…The compounds behind these predictions all featured multiple stereo-centers, but the descriptor set used to encode the structures for the QSAR modeling is achiral. Leach et al [44] have recently shown that protein binding is affected by stereochemistry. The mispredictions were caused by diastereoisomers with identical descriptor representations but different 3-dimensional shapes, and therefore different levels of protein binding.…”

Chiral Pharmaceuticals in Diverse Environmental Matrices: Occurrence, Removal and Toxicity

“…28 Os enantiômeros de FQ têm diferenças na farmacocinética, farmacodinâmica, toxicologia e ecotoxicologia, podendo afetar de forma diferente os organismos aquáticos. 29,30 Os FQ com diferentes propriedades farmacocinéticas e farmacodinâmicas têm diferentes constantes de dissociação do local de ligação. Isso leva à resposta biológica diferente, 31 [31][32][33][34][35][36][37] As vantagens de formulações enantiomericamente puras são menor dose terapêutica, maior margem de segurança, menor variabilidade interindividual, menos interações medicamentosas e efeitos secundários.…”

Optical Isomerism in Drugs

“…Besides the difference in potency, it often happens that two enantiomers show differences in their pharmacological profile [42,43]. In such a case, resolving the racemic mixture can generate two pharmacologically different and useful compounds, and can also separate the more active compound from its less well tolerated or more toxic isomer.…”