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Creator |
c3fb382d8485dab4cd59eb0e02f58fdb |
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Creator |
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Creator |
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Creator |
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Creator |
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Creator |
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Creator |
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Creator |
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Creator |
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Creator |
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Creator |
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Creator |
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Creator |
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Creator |
ext-d0b0a50756479752b955ec4c2537cb36 |
| 38118 |
Date |
2011 |
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Is Part Of |
repository |
| 38118 |
Is Part Of |
p15204804 |
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abstract |
We report the syntheses and activities of a wide range of thiazolides [viz., 2-hydroxyaroyl-N-(thiazol-2-yl)amides]
against hepatitis B virus replication, with QSAR analysis of our results. The prototypical
thiazolide, nitazoxanide [2-hydroxybenzoyl-<i>N</i>-(5-nitrothiazol-2-yl)amide, NTZ]
1 is a broad spectrum antiinfective agent effective against anaerobic bacteria, viruses,
and parasites. By contrast, 2-hydroxybenzoyl-N-(5-chlorothiazol-2-yl)amide 3 is a
novel, potent, and selective inhibitor of hepatitis B replication (EC<sub>50</sub>
= 0.33 <i>μ</i>m) but is inactive against anaerobes. Several 4<i>'</i>- and 5<i>'</i>-substituted
thiazolides show good activity against HBV; by contrast, some related salicyloylanilides
show a narrower spectrum of activity. The ADME properties of 3 are similar to 1; viz.,
the <i>O</i>-acetate is an effective prodrug, and the <i>O</i>-aryl glucuronide is
a major metabolite. The QSAR study shows a good correlation of observed EC<sub>90</sub>
for intracellular virions with thiazolide structural parameters. Finally we discuss
the mechanism of action of thiazolides in relation to the present results. |
| 38118 |
authorList |
authors |
| 38118 |
issue |
12 |
| 38118 |
status |
peerReviewed |
| 38118 |
volume |
54 |
| 38118 |
type |
AcademicArticle |
| 38118 |
type |
Article |
| 38118 |
label |
Stachulski, Andrew V.; Pidathala, Chandrakala; Row, Eleanor C.; Sharma, Raman;
Berry, Neil G.; Iqbal, Mazhar; Bentley, Joanne; Allman, Sarah A. ; Edwards, Geoffrey;
Helm, Alison; Hellier, Jennifer; Korba, Brent E.; Semple, J. Edward and Rossignol,
Jean-Francois (2011). Thiazolides as novel antiviral agents. 1. Inhibition of hepatitis
B virus replication. Journal of Medicinal Chemistry, 54(12) pp. 4119–4132. |
| 38118 |
label |
Stachulski, Andrew V.; Pidathala, Chandrakala; Row, Eleanor C.; Sharma, Raman; Berry,
Neil G.; Iqbal, Mazhar; Bentley, Joanne; Allman, Sarah A. ; Edwards, Geoffrey; Helm,
Alison; Hellier, Jennifer; Korba, Brent E.; Semple, J. Edward and Rossignol, Jean-Francois
(2011). Thiazolides as novel antiviral agents. 1. Inhibition of hepatitis B virus
replication. Journal of Medicinal Chemistry, 54(12) pp. 4119–4132. |
| 38118 |
sameAs |
jm200153p |
| 38118 |
Title |
Thiazolides as novel antiviral agents. 1. Inhibition of hepatitis B virus replication |
| 38118 |
in dataset |
oro |