| Compound Info | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| NAs | Base Info | ||||||||
| ID | Cluster | Name | Target | MolWt | |||||
|
NAs.003536 | 0 |
|
554.242 | |||||
| Chemical Representations | |
|---|---|
| InChI | InChI=1S/C14H17N6O12P3/c1-13(5-15)11(21)9(4-29-34(25,26)32-35(27,28)31-33(22,23)24)30-14(13,6-16)10-3-2-8-12(17)18-7-19-20(8)10/h2-3,7,9,11,21H,4H2,1H3,(H,25,26)(H,27,28)(H2,17,18,19)(H2,22,23,24)/t9-,11+,13-,14+/m0/s1 |
| InChI Key | YIBIPPFJFSDBAG-PCGAWMICSA-N |
| SMILES | C[C@]1(C#N)[C@H](O)[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O[C@]1(C#N)c1ccc2c(N)ncnn12 |
| Molecular Formula | C14H17N6O12P3 |
| Functional Fragments | ||
|---|---|---|
| Base | Ribose | Phosphate |
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| Calculated Properties | ||
|---|---|---|
| logP | -0.337 | Computed by RDKit |
| Heavy Atom Count | 35 | Computed by RDKit |
| Ring Count | 3 | Computed by RDKit |
| Hydrogen Bond Acceptor Count | 14 | Computed by RDKit |
| Hydrogen Bond Donor Count | 6 | Computed by RDKit |
| Rotatable Bond Count | 8 | Computed by RDKit |
| Topological Polar Surface Area | 293.070 | Computed by RDKit |
| Activity Data | ||||||
|---|---|---|---|---|---|---|
| Target | Activity type | Relation | Value | Unit | Assay | Source |
| Genome polyprotein | IC50 | = | 1200.0 | nM | Inhibition Assay: To measure inhibition of the enzymatic activity of the HCV NS5B RNA-dependent RNA polymerase by the nucleoside triphosphate compounds of the present invention, a radiolabeled nucleotide incorporation assay was used. This assay is a modified version of the assay described in International Publication No. WO2002/057287. Briefly, 50 uL reactions containing 20 mM HEPES (pH 7.3); 7.5 mM DTT; 20 units/ml RNasIN; 1 uM each of ATP, GTP, UTP and CTP; 20 uCi/mL [33P]-CTP; 10 mM MgCl; 60 mM NaCl; 100 ug/ml BSA; 0.021 uM DCoH heteropolymer RNA template; and 5 nM NS5B (1b-BKΔ55) enzyme were incubated at room temperature for 1 hour. The assay was then terminated by the addition of 500 mM EDTA (50 uL). The reaction mixture was transferred to a Millipore DE81 filter plate and the incorporation of labeled CTP is determined using Packard TopCount. Compound IC50 values can then be calculated from experiments with 10 serial 3-fold dilutions of the inhibitor in duplicate. The intrinsic potency (Ki) of an NTP inhibitor is derived from its NS5B IC50 using the Cheng-Prusoff equation for a competitive inhibitor, as described in Cheng et al., Biochem Pharmacol 22:3099-3108 (1973): Ki=IC50/(1+[S]/Km), where [S]=1 uM, and Km is the concentration of cognate NTP yielding half-maximal enzyme activity in the assay absent exogenous inhibitors. | CHEMBL3886494 |