Deuterated Drugs

Recent Updates on the Development of Deuterium-Containing Drugs for the Treatment of Cancer

“…The KIE is the change of chemical reaction rate when one of the atoms in a compound is substituted by its isotopes. 18 Due to the higher molecular weight of deuterium, C-D bonds have a lower vibrational frequency and zero-point energy and needs higher activation energy that decreases the rate (k) of C-D bond cleavage. This rate effect is the deuterium isotope effect (DIE) and is expressed as kH/kD the ratio of the rate of C-H vs C-D bond cleavage.…”

“…However, minor shifts in physical properties such as reduced hydrophobicity and altered pKa for acids and bases are insignificant to affect the potency or selectivity of the targets. 18 , 19 …”

“…However, minor shifts in physical properties such as reduced hydrophobicity and altered pKa for acids and bases are insignificant to affect the potency or selectivity of the targets. 18,19 Deuteration of drugs reduces the metabolic rate (especially oxidative) in the gut wall or liver, which causes the parent drug to enter into the systemic circulation or increases the bioavailability of the parent drug. In most cases, the systemic clearance rate is unaffected.…”

Impact of multiple H/D replacements on the physicochemical properties of flurbiprofen

“…The differential strength between the C-D and C-H bonds has led to the development of deuterated drugs. [4][5][6] In most cases, drug metabolism is triggered by the oxidative cleavage of the C-H bond by cytochrome P450 (CYP). Therefore, the replacement of C-H bonds with stable C-D bonds at a CYPmediated metabolic site suppresses metabolism in the small intestine epithelial cells and liver and enhances the pharmacokinetic property of changing the pharmacological parameters of drugs.…”

Vitamin B12‐Photocatalyzed Cyclopropanation of Electron‐Deficient Alkenes Using Dichloromethane as the Methylene Source**

“…[51] Deuteration of small-molecule drugs has been shown to favorably affect their pharmacokinetic properties. [52] Consequently, the metabolism of certain drugs may be positively influenced upon deuterium incorporation, resulting in improved safety, tolerability, or efficacy. [53,54] Therefore, we envisioned that by starting with readily available CD 2 Cl 2 , our Vitamin B 12 -photocatalyzed cyclopropanation could offer a facile and inexpensive means for late-stage deuterium incorporation into pharmaceutically active compounds.…”