| Compound Info | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| NAs | Base Info | ||||||||
| ID | Cluster | Name | Target | MolWt | |||||
|
NAs.003596 | 0 |
|
559.258 | |||||
| Chemical Representations | |
|---|---|
| InChI | InChI=1S/C14H20N5O13P3/c1-13(6-15)11(20)9(5-29-34(24,25)32-35(26,27)31-33(21,22)23)30-14(13,28-2)10-4-3-8-12(16)17-7-18-19(8)10/h3-4,7,9,11,20H,5H2,1-2H3,(H,24,25)(H,26,27)(H2,16,17,18)(H2,21,22,23)/t9-,11-,13-,14+/m0/s1 |
| InChI Key | SFUFZFGZNMYWEU-DTCNJJKHSA-N |
| SMILES | CO[C@]1(c2ccc3c(N)ncnn23)O[C@@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@H](O)[C@]1(C)C#N |
| Molecular Formula | C14H20N5O13P3 |
| Functional Fragments | ||
|---|---|---|
| Base | Ribose | Phosphate |
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| Calculated Properties | ||
|---|---|---|
| logP | -0.256 | 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 | 9 | Computed by RDKit |
| Topological Polar Surface Area | 278.510 | Computed by RDKit |
| Activity Data | ||||||
|---|---|---|---|---|---|---|
| Target | Activity type | Relation | Value | Unit | Assay | Source |
| Genome polyprotein | IC50 | = | 87.0 | 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 |