2fvc: Difference between revisions

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==Overview==

Recently, we disclosed a new class of HCV polymerase inhibitors discovered, through high-throughput screening (HTS) of the GlaxoSmithKline proprietary, compound collection. This interesting class of, 3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones, potently inhibits HCV polymerase enzymatic activity and inhibits the, ability of the subgenomic HCV replicon to replicate in Huh-7 cells. This, report will focus on the structure-activity relationships (SAR) of, substituents on the quinolinone ring, culminating in the discovery of, 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluor, o-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent potency, in biochemical and cellular assays possessing attractive molecular, properties for advancement as a clinical candidate. The potential for, development and safety assessment profile of compound 130 will also be, discussed.

Recently, we disclosed a new class of HCV polymerase inhibitors discovered through high-throughput screening (HTS) of the GlaxoSmithKline proprietary compound collection. This interesting class of 3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones potently inhibits HCV polymerase enzymatic activity and inhibits the ability of the subgenomic HCV replicon to replicate in Huh-7 cells. This report will focus on the structure-activity relationships (SAR) of substituents on the quinolinone ring, culminating in the discovery of 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluor o-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent potency in biochemical and cellular assays possessing attractive molecular properties for advancement as a clinical candidate. The potential for development and safety assessment profile of compound 130 will also be discussed.

==About this Structure==

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[[Category: Hepatitis c virus subtype 1b]]

[[Category: Single protein]]

[[Category: Concha, N.O.]]

[[Category: Concha, N O.]]

[[Category: Singh, O.]]

[[Category: Wonacott, A.]]

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[[Category: thiadiazin inhibitor]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:25:26 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-Recently, we disclosed a new class of HCV polymerase inhibitors discovered, through high-throughput screening (HTS) of the GlaxoSmithKline proprietary, compound collection. This interesting class of, 3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones, potently inhibits HCV polymerase enzymatic activity and inhibits the, ability of the subgenomic HCV replicon to replicate in Huh-7 cells. This, report will focus on the structure-activity relationships (SAR) of, substituents on the quinolinone ring, culminating in the discovery of, 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluor, o-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent potency, in biochemical and cellular assays possessing attractive molecular, properties for advancement as a clinical candidate. The potential for, development and safety assessment profile of compound 130 will also be, discussed.
+Recently, we disclosed a new class of HCV polymerase inhibitors discovered through high-throughput screening (HTS) of the GlaxoSmithKline proprietary compound collection. This interesting class of 3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones potently inhibits HCV polymerase enzymatic activity and inhibits the ability of the subgenomic HCV replicon to replicate in Huh-7 cells. This report will focus on the structure-activity relationships (SAR) of substituents on the quinolinone ring, culminating in the discovery of 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluor o-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent potency in biochemical and cellular assays possessing attractive molecular properties for advancement as a clinical candidate. The potential for development and safety assessment profile of compound 130 will also be discussed.
 ==About this Structure==
@@ Line 13: / Line 13: @@
 [[Category: Hepatitis c virus subtype 1b]]
 [[Category: Single protein]]
-[[Category: Concha, N.O.]]
+[[Category: Concha, N O.]]
 [[Category: Singh, O.]]
 [[Category: Wonacott, A.]]
@@ Line 20: / Line 20: @@
 [[Category: thiadiazin inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 19:45:25 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:25:26 2008''