DDD85646 (DDD-85646) is a novel and potent inhibitor of T. brucei N-myristoyltransferase (TbNMT) with an apparent Ki value of 1.44 nM. DDD85646 has potent activity against the enzyme (IC(50) = 2 nM) and T. brucei (EC(50) = 2 nM) in culture. DDD85646 has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. DDD85646 provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.
Physicochemical Properties
| Molecular Formula | C21H24CL2N6O2S |
| Molecular Weight | 495.425260543823 |
| Exact Mass | 494.105 |
| Elemental Analysis | C, 50.91; H, 4.88; Cl, 14.31; N, 16.96; O, 6.46; S, 6.47 |
| CAS # | 1215010-55-1 |
| PubChem CID | 44199337 |
| Appearance | Solid powder |
| Density | 1.5±0.1 g/cm3 |
| Boiling Point | 684.3±65.0 °C at 760 mmHg |
| Flash Point | 367.6±34.3 °C |
| Vapour Pressure | 0.0±2.1 mmHg at 25°C |
| Index of Refraction | 1.693 |
| LogP | 2.28 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 32 |
| Complexity | 722 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | ClC1C=C(C=C(C=1S(NC1C(C)=NN(C)C=1C)(=O)=O)Cl)C1C=CN=C(C=1)N1CCNCC1 |
| InChi Key | XMBSZPZJLPTFMV-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H24Cl2N6O2S/c1-13-20(14(2)28(3)26-13)27-32(30,31)21-17(22)10-16(11-18(21)23)15-4-5-25-19(12-15)29-8-6-24-7-9-29/h4-5,10-12,24,27H,6-9H2,1-3H3 |
| Chemical Name | 2,6-dichloro-4-[2-(1-piperazinyl)-4-pyridinyl]-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)-benzenesulfonamide |
| Synonyms | DDD-85646; DDD85646; DDD 85646. |
| 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
| References | :J Med Chem. 2017 Nov 10. doi: 10.1021/acs.jmedchem.7b01255. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~201.84 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.05 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 25.0 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: ≥ 2.5 mg/mL (5.05 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0184 mL | 10.0922 mL | 20.1845 mL | |
| 5 mM | 0.4037 mL | 2.0184 mL | 4.0369 mL | |
| 10 mM | 0.2018 mL | 1.0092 mL | 2.0184 mL |