2013
DOI: 10.1021/jm301643a
|View full text |Cite
|
Sign up to set email alerts
|

Structure-Based Discovery of Pyrazolobenzothiazine Derivatives As Inhibitors of Hepatitis C Virus Replication

Abstract: The NS5B RNA-dependent RNA polymerase is an attractive target for the development of novel and selective inhibitors of hepatitis C virus replication. In order to identify novel structural hits as anti-HCV agents, we performed structure-based virtual screening of our in-house library followed by rational drug design, organic synthesis and biological testing. These studies led to the identification of pyrazolobenzothiazine scaffold as a suitable template for obtaining novel anti-HCV agents targeting the NS5B pol… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1

Citation Types

2
43
0

Year Published

2015
2015
2022
2022

Publication Types

Select...
7
1

Relationship

1
7

Authors

Journals

citations
Cited by 41 publications
(45 citation statements)
references
References 37 publications
2
43
0
Order By: Relevance
“…(a): (5e19) (i) 1,1 0 -carbonyldiimidazole, anhydrous THF, 25 C, 3 h; (ii) aniline (5,6,13,14), 4-chloroaniline (7,8,9,15,16,17) Cells were harvested and processed for total RNA isolation and one step qRT-PCR. *p < 0.05; **p < 0.01.…”
Section: Inhibition Of Hcv Ns5b Rdrpmentioning
confidence: 99%
See 1 more Smart Citation
“…(a): (5e19) (i) 1,1 0 -carbonyldiimidazole, anhydrous THF, 25 C, 3 h; (ii) aniline (5,6,13,14), 4-chloroaniline (7,8,9,15,16,17) Cells were harvested and processed for total RNA isolation and one step qRT-PCR. *p < 0.05; **p < 0.01.…”
Section: Inhibition Of Hcv Ns5b Rdrpmentioning
confidence: 99%
“…Found: C, 65.96%; H, 4.12%, N, 15.19%; Cl, 9.61%.5.1.9. 1-(4-Chlorophenyl)-4-cyano-N-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide(13) …”
mentioning
confidence: 99%
“…Therefore, this route was a small scale only for the construction of diversified compound libraries. (Scheme 27)After performing structure-based virtual screening of their in-house library followed by rational drug design, organic synthesis, and biological testing, Barreca et al[77] 148 was the best NS5B polymerase inhibitor, which not only had relatively good affinity and inhibitory effects in both enzymatic and replicon assays, but also exhibited the significant activities (EC50 = 3.6 µM, EC 90 = 25.6 µM and CC 50 > 180 µM) in the Huh 9−13 replicon system, thus providing a good starting point for further hit evolution. Its preparation started from 145.…”
mentioning
confidence: 99%
“…Various pyrazolobenzothiazine derivatives have been reported to be antipyretic, analgesic and anti-inflammatory, 1,2 antihypertensive, 3 anti-depressant, 4 anti-oxidant and antibacterial agents. 5,6 Recently, compounds based on this ring system have been reported as inhibitors of HCV replication (a, Figure 1) 7 and as anti-HIV agents (b, Figure 1). 8 Other derivatives of benzothiazines have been reported to act as anti-inflammatory, 9 antimalarial, 10 antiallergic, 11 antithrombotic, 12 antidepressants 13 and antibacterial agents.…”
mentioning
confidence: 99%
“…Structures of antiviral agents belonging to pyrazolobenzothiazine ring system. 7,8 Human immunodeficiency virus (HIV) is responsible for Acquired Immunodeficiency Syndrome (AIDS) and is treated [1,2]benzothiazin-2(4H)-yl)acetamides were screened for anti-HIV-1 activity and cytotoxicity. The compounds 6a, 6d, 6e, 6g and 6i from the series 6a-i of benzylamides and 7a, 7b, 7c, 7d and 7e from the series 7a-f of anilides were identified as effective anti-HIV-1 agents with EC50 values < 20 µM.…”
mentioning
confidence: 99%