PMID- 31138367
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20200330
IS  - 0031-7144 (Print)
IS  - 0031-7144 (Linking)
VI  - 74
IP  - 6
DP  - 2019 Jun 1
TI  - Discovery and Structure-Resistance Relationship Study of New Thieno[2,3-b] 
      Pyridine HCV NS4B Inhibitors.
PG  - 321-325
LID - 10.1691/ph.2019.8960 [doi]
AB  - The non-structural protein 4B (NS4B) of hepatitis C virus (HCV) has emerged as a 
      promising target for chronic hepatitis C treatment. The thieno[2,3-b]pyridine HCV 
      inhibitor 2 has demonstrated properties as a NS4B inhibitor. Subsequent 
      hybridization of 2 with our recently published imidazo[2,1-b]thiazole NS4B 
      inhibitor 3 resulted in the discovery of several more potent compounds with 
      sub-micromolar EC(50) against HCV genotype 1b replicon. More importantly, the 
      resistant profile study of the new synthesized HCV inhibitors illustrated that 
      the bicyclic scaffold would mediate the resistance of H3R and Q26R mutations, 
      while the piperazinone motif would mediate the resistance of H94R, F98C and V105M 
      mutations, and the C3- amino group would disrupt the interaction between 
      piperazinone motif and NS4B. This structure-resistance relationship detail could 
      help us to develop new NS4B inhibitors with higher resistant barrier in the 
      future.
FAU - Xiao, Kun-Jie
AU  - Xiao KJ
FAU - Zuo, Wei-Qiong
AU  - Zuo WQ
FAU - Xu, Ying
AU  - Xu Y
FAU - Tao, Xin
AU  - Tao X
FAU - Yu, Luo-Ting
AU  - Yu LT
FAU - Wang, Ning-Yu
AU  - Wang NY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Pharmazie
JT  - Die Pharmazie
JID - 9800766
RN  - 0 (Antiviral Agents)
RN  - 0 (Pyridines)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Antiviral Agents/*chemistry
MH  - Hepacivirus
MH  - Humans
MH  - Pyridines/*chemistry/*pharmacology
MH  - Viral Nonstructural Proteins/*antagonists & inhibitors
MH  - Virus Replication/drug effects
EDAT- 2019/05/30 06:00
MHDA- 2020/03/31 06:00
CRDT- 2019/05/30 06:00
PHST- 2019/05/30 06:00 [entrez]
PHST- 2019/05/30 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
AID - 10.1691/ph.2019.8960 [doi]
PST - ppublish
SO  - Pharmazie. 2019 Jun 1;74(6):321-325. doi: 10.1691/ph.2019.8960.