InChI=1S/C22H21NO3S/c1- 14(2)23(21(24)17-11-9-15(3)10-12-17)18-13-19(27-20(18)22(25)26)16-7-5-4-6-8-16/h4-14H,1-3H3,(H,25,26) |
| LRHXIDOGMBZJFN-UHFFFAOYSA-N |
| CC(C)N(C(=O)c1ccc(C)cc1)c1cc(sc1C(O)=O)-c1ccccc1 |
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EC 2.7.7.6 (RNA polymerase) inhibitor
An EC 2.7.7.* (nucleotidyltransferase) inhibitor that interferes with the action of RNA polymerase (EC 2.7.7.6).
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View more via ChEBI Ontology
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Outgoing
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3-[isopropyl(4-methylbenzoyl)amino]-5-phenylthiophene-2-carboxylic acid
(CHEBI:43541)
has role
EC 2.7.7.6 (RNA polymerase) inhibitor
(CHEBI:37416)
3-[isopropyl(4-methylbenzoyl)amino]-5-phenylthiophene-2-carboxylic acid
(CHEBI:43541)
is a
monocarboxylic acid amide
(CHEBI:29347)
3-[isopropyl(4-methylbenzoyl)amino]-5-phenylthiophene-2-carboxylic acid
(CHEBI:43541)
is a
thiophenes
(CHEBI:26961)
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3-[(4-methylbenzoyl)(propan-2-yl)amino]-5-phenylthiophene-2-carboxylic acid
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3-[ISOPROPYL(4-METHYLBENZOYL)AMINO]-5-PHENYLTHIOPHENE-2-CARBOXYLIC ACID
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PDBeChem
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3-[isopropyl(4-methylbenzoyl)amino]-5-phenylthiophene-2-carboxylic acid
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ChEBI
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3-[Isopropyl-(4-methyl-benzoyl)-amino]-5-phenyl-thiophene-2-carboxylic acid
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ChEMBL
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9651127
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Beilstein Registry Number
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Beilstein
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Biswal BK, Cherney MM, Wang M, Chan L, Yannopoulos CG, Bilimoria D, Nicolas O, Bedard J, James MN (2005)
Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus reveal two conformations and suggest mechanisms of inhibition by non-nucleoside inhibitors.
The Journal of biological chemistry 280, 18202-18210 [PubMed:15746101]
[show Abstract]
Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus (HCV) from two crystal forms have been determined. Similar to the three-dimensional structures of HCV polymerase genotype 1b and other known polymerases, the structures of the HCV polymerase genotype 2a in both crystal forms can be depicted in the classical right-hand arrangement with fingers, palm, and thumb domains. The main structural differences between the molecules in the two crystal forms lie at the interface of the fingers and thumb domains. The relative orientation of the thumb domain with respect to the fingers and palm domains and the beta-flap region is altered. Structural analysis reveals that the NS5B polymerase in crystal form I adopts a "closed" conformation that is believed to be the active form, whereas NS5B in crystal form II adopts an "open" conformation and is thus in the inactive form. In addition, we have determined the structures of two NS5B polymerase/non-nucleoside inhibitor complexes. Both inhibitors bind at a common binding site, which is nearly 35 A away from the polymerase active site and is located in the thumb domain. The binding pocket is predominantly hydrophobic in nature, and the enzyme inhibitor complexes are stabilized by hydrogen bonding and van der Waals interactions. Inhibitors can only be soaked in crystal form I and not in form II; examination of the enzyme-inhibitor complex reveals that the enzyme has undergone a dramatic conformational change from the form I (active) complex to the form II (inactive). | Chan L, Pereira O, Reddy TJ, Das SK, Poisson C, Courchesne M, Proulx M, Siddiqui A, Yannopoulos CG, Nguyen-Ba N, Roy C, Nasturica D, Moinet C, Bethell R, Hamel M, L'Heureux L, David M, Nicolas O, Courtemanche-Asselin P, Brunette S, Bilimoria D, Bédard J (2004)
Discovery of thiophene-2-carboxylic acids as potent inhibitors of HCV NS5B polymerase and HCV subgenomic RNA replication. Part 2: tertiary amides.
Bioorganic & medicinal chemistry letters 14, 797-800 (Source: ChEMBL) [PubMed:14741292]
[show Abstract]
Further SAR studies on the thiophene-2-carboxylic acids are reported. These studies led to the identification of a series of tertiary amides that show inhibition of both HCV NS5B polymerase in vitro and HCV subgenomic RNA replication in Huh-7 cells. Structural insights about the bioactive conformation of this class of molecules were deduced from a combination of modeling and transferred NOE (trNOE) studies. |
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