Header
Header
Article

Synthesis and biological evaluation of deuterated sofosbuvir analogs as HCV NS5B inhibitors with enhanced pharmacokinetic properties.

Icon for Wiley Related Articles

Synthesis and biological evaluation of deuterated sofosbuvir analogs as HCV NS5B inhibitors with enhanced pharmacokinetic properties.

J Labelled Comp Radiopharm. 2019 Mar 03;:

Authors: Ao W, Ma X, Lin Y, Wang X, Song W, Wang Q, Zhang X, Xu H, Zhang Y

Abstract
A series of deuterated sofosbuvir analogs were designed and prepared with the aim of improving their pharmacokinetic properties. The devised synthetic routes allow for site-selective deuterium incorporation with high levels of isotopic purity. As expected, the deuterated analogs (37-44) are as efficacious as sofosbuvir when tested in vitro inhibition of viral replication (replicon) assays. Compared to sofosbuvir, deuterated analog 40 displays improved in vivo pharmacokinetics profiles in rats and dogs in terms of the metabolite and the prodrug. The Cmax and AUC of 40 in dogs were increased by 3.4 and 2.7 fold, respectively. Due to the enhanced pharmacokinetic properties and the great synthetic advantage of an inexpensive deuterium source (D2 O) for 40, it was chosen for further investigation.

PMID: 30827031 [PubMed – as supplied by publisher]

Source link

Back to top button