Identification of 1-isopropylsulfonyl-2-amine benzimidazoles as a new class of inhibitors of hepatitis B virus.
A series of 1-isopropylsulfonyl-2-amine benzimidazole derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in the HepG2.2.15 cell line. In general, these derivatives are potent HBV inhibitors (IC(50)<4 microM) with high selectivity indices (SIs>40). Compounds 5b-e, g, j, and 9a were among the most prominent compounds, with IC(50)s of 0.70-2.0 microM and SIs of 41-274. The potent anti-HBV activity and safety profiles of the most promising compounds 5d and j (IC(50)s=0.70 microM, SIs>120) demonstrate the potential of this series of benzimidazoles for the development of new anti-HBV drugs.
Li
Yun-Fei
YF
Institute of Medicinal Chemistry, Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai, Shanghai 200062, China.
Wang
Gui-Feng
GF
Luo
Yu
Y
Huang
Wei-Gang
WG
Tang
Wei
W
Feng
Chun-Lan
CL
Shi
Li-Ping
LP
Ren
Yu-Dan
YD
Zuo
Jian-Ping
JP
Lu
Wei
W
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50
D001562:Benzimidazoles; D004279:DNA, Viral; C031000:benzimidazole