ABT-072 is a novel and potent nonnucleoside NS5B polymerase inhibitor and a candidate drug evaluated for treatment of hepatitis C virus (HCV).
Physicochemical Properties
| Molecular Formula | C24H27N3O5S |
| Molecular Weight | 469.553284883499 |
| Exact Mass | 469.167 |
| Elemental Analysis | C, 61.39; H, 5.80; N, 8.95; O, 17.04; S, 6.83 |
| CAS # | 1132936-00-5 |
| Related CAS # | ABT-072 potassium trihydrate;1132940-31-8 |
| PubChem CID | 57775240 |
| Appearance | Off-white to yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Index of Refraction | 1.625 |
| LogP | 3.64 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 33 |
| Complexity | 879 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CS(=O)(NC1=CC=C(/C=C/C2=CC(N(C(N3)=O)C=CC3=O)=CC(C(C)(C)C)=C2OC)C=C1)=O |
| InChi Key | XMZSTQYSBYEENY-RMKNXTFCSA-N |
| InChi Code | InChI=1S/C24H27N3O5S/c1-24(2,3)20-15-19(27-13-12-21(28)25-23(27)29)14-17(22(20)32-4)9-6-16-7-10-18(11-8-16)26-33(5,30)31/h6-15,26H,1-5H3,(H,25,28,29)/b9-6+ |
| Chemical Name | (E)-N-(4-(3-(tert-butyl)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxystyryl)phenyl)methanesulfonamide |
| Synonyms | ABT-072; ABT 072; ABT072. |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | NS5B polymerase |
| ln Vitro | ABT-072 is a non-nucleoside inhibitor of NS5B polymerase that exhibits nanomolar potency against hepatitis C virus polymerases of genotypes 1a and 1b in vitro[1]. |
| ln Vivo | Good PK properties are shown by ABT-072 (5 and/or 30 mg/kg; i.v. or p.o.). In vitro or oral ABT-072 (2.5 and/or 30 mg/kg) exhibits high oral bioavailability and low plasma clearance[3]. |
| Animal Protocol |
Animal Model: Rats[3] Dosage: 5 and/or 30 mg/kg (Pharmacokinetic Analysis) Administration: I.v. or p.o. Result: Showed good PK properties. |
| References |
[1]. A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1. J Hepatol. 2013;59(1):18-23. [2]. Assessing Supersaturation and Its Impact on In Vivo Bioavailability of a Low-Solubility Compound ABT-072 With a Dual pH, Two-Phase Dissolution Method. J Pharm Sci. 2016;105(9):2886-2895. [3]. Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability. J Med Chem. 2018;61(3):1153-1163. [4]. US 20120196794 A1 |
| Additional Infomation | ABT-072 is under investigation in clinical trial NCT00890318 (A Study in Healthy Adult Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetic Profiles of Multiple Doses of ABT-072 Used to Treat Hepatitis C). |
Solubility Data
| Solubility (In Vitro) | DMSO : ~80 mg/mL (~170.38 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4 mg/mL (8.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 40.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 4 mg/mL (8.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 40.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 4 mg/mL (8.52 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 40.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 4 mg/mL (8.52 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1297 mL | 10.6485 mL | 21.2970 mL | |
| 5 mM | 0.4259 mL | 2.1297 mL | 4.2594 mL | |
| 10 mM | 0.2130 mL | 1.0648 mL | 2.1297 mL |