Highly suppressing wild-type HIV-1 and Y181C mutant HIV-1 strains by 10-chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile

  • J Med Chem. 2010 Feb 11;53(3):1397-401. doi: 10.1021/jm901653e.
Hai Xue  1 ,  Xiaofan Lu ,  Purong Zheng ,  Li Liu ,  Chunyan Han ,  Jinping Hu ,  Zijie Liu ,  Tao Ma ,  Yan Li ,  Lin Wang ,  Zhiwei Chen ,  Gang Liu
Affiliations
  • 1. Department of Synthetic Medicinal Chemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 2 Nan Wei Road, Beijing 100050, China.
PMID: 20050672 DOI: 10.1021/jm901653e
Abstract

We herein report a new compound: 10-chloromethyl-11-demethyl-12-oxo-calanolide A (20, EC(50) = 7.4 nM, SI = 1417), which demonstrates a druggable profile with 32.7% oral bioavailability in rat, tolerated oral single dose toxicity in mice, and especially the feature of highly efficient suppression of the wild-type HIV-1 and Y181C mutant HIV-1 at an EC(50) = 7.4 nM and EC(50) = 0.46 nM, respectively.