Structural development studies of anti-hepatitis C virus agents with a phenanthridinone skeleton

Masahiko Nakamura; Atsushi Aoyama; Mohammed T A Salim; Mika Okamoto; Masanori Baba; Hiroyuki Miyachi; Yuichi Hashimoto; Hiroshi Aoyama

doi:10.1016/j.bmc.2010.02.057

Structural development studies of anti-hepatitis C virus agents with a phenanthridinone skeleton

Bioorg Med Chem. 2010 Apr 1;18(7):2402-11. doi: 10.1016/j.bmc.2010.02.057. Epub 2010 Mar 2.

Authors

Masahiko Nakamura¹, Atsushi Aoyama, Mohammed T A Salim, Mika Okamoto, Masanori Baba, Hiroyuki Miyachi, Yuichi Hashimoto, Hiroshi Aoyama

Affiliation

¹ Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

PMID: 20303772
DOI: 10.1016/j.bmc.2010.02.057

Abstract

A phenanthridinone skeleton was derived from our previous researches on thalidomide and retinoids as a multi-template for generation of anti-viral lead compounds. Structural development studies focusing on anti-hepatitis C virus activity afforded 5-butyl-2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenanthridin-6(5H)-one (10) and 5-butylbenzo[b]phenanthridin-6(5H)-one (39), which showed EC(50) values of approximately 3.7 and 3.2microM, respectively.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / chemical synthesis*
Antiviral Agents / pharmacology*
Cell Line
Diarrhea Virus 1, Bovine Viral / drug effects
Drug Design
Gene Expression Regulation, Viral / drug effects
Glyceraldehyde-3-Phosphate Dehydrogenases / biosynthesis
Hepacivirus / drug effects*
Hepacivirus / genetics
Humans
Indicators and Reagents
Magnetic Resonance Spectroscopy
Mass Spectrometry
Phenanthridines / chemical synthesis*
Phenanthridines / pharmacology*
RNA, Viral / biosynthesis
RNA, Viral / drug effects
Stereoisomerism
Structure-Activity Relationship

Substances

Antiviral Agents
Indicators and Reagents
Phenanthridines
RNA, Viral
Glyceraldehyde-3-Phosphate Dehydrogenases