Deuterium is the stable isotope of hydrogen which has been applied in mechanistic, spectroscopic and tracer studies. To medicinal chemist, the size and shape of deuterium are essentially identical to that of hydrogen atom within a drug molecule which can retain its biological activity and selectivity when the hydrogen is replaced by the deuterium. On the other hand, the C-D bond is stronger than the C-H bond; the increased bond strength can positively impact certain drugs’ absorption, distribution, metabolism and excretion (ADME) properties, and also can potential improve drug efficacy, safety and tolerability. Deuteration has been widely used in human clinical studies, such as pharmacokinetic and metabolic studies, which has gained traction since it becomes more and more difficult to discover a new drug by existing models. Herein we report the synthesis of several deuterated combinatorial libraries, such as deuterated oxybutynins, deuterated atorvastatins and deuterated sorafenibs; all the D-compounds have been characterized by MS and 1H NMR and some examples are shown in Table 1. Some these D-compounds have been screened for their biological activities, such as antitumor.

Deuteration in drug discovery

251st National Meeting (2016)

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