TBAJ-587, a diarylquinoline analog, is a novel and potent anti-tuberculosis agent which inhibits M.tb strain H37Rv growth with MIC90s of 0.006 and<0.02 µg/mL in MABA and LORA assay, respectively. It demonstrated more potent in vitro and in vivo anti-tubercular activity, with greatly attenuated hERG blockade. It is as potent as bedaquiline against Mycobacterium tuberculosis, but with lower lipophilicity, higher clearance, and lower risk for QT prolongation. TBAJ-587 inhibits hERG channel minimally, attenuates inhibition of the cardiac potassium channel protein coded by the hERG, which is important for cardiac repolarization.
Physicochemical Properties
| Molecular Formula | C30H33BRFN3O5 |
| Molecular Weight | 614.502530813217 |
| Exact Mass | 613.16 |
| Elemental Analysis | C, 58.64; H, 5.41; Br, 13.00; F, 3.09; N, 6.84; O, 13.02 |
| CAS # | 2252316-16-6 |
| Related CAS # | 2252316-16-6;TBAJ-587 HCl; |
| PubChem CID | 138319677 |
| Appearance | Solid powder |
| LogP | 5.6 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 40 |
| Complexity | 774 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CN(C)CC[C@@](C1=CC(=NC(=C1)OC)OC)([C@H](C2=C(C(=CC=C2)OC)F)C3=C(N=C4C=CC(=CC4=C3)Br)OC)O |
| InChi Key | JJEGOJPMKLRSPJ-POURPWNDSA-N |
| InChi Code | InChI=1S/C30H33BrFN3O5/c1-35(2)13-12-30(36,19-16-25(38-4)34-26(17-19)39-5)27(21-8-7-9-24(37-3)28(21)32)22-15-18-14-20(31)10-11-23(18)33-29(22)40-6/h7-11,14-17,27,36H,12-13H2,1-6H3/t27-,30-/m1/s1 |
| Chemical Name | (1S,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-2-(2,6-dimethoxypyridin-4-yl)-4-(dimethylamino)-1-(2-fluoro-3-methoxyphenyl)butan-2-ol |
| Synonyms | TBAJ-587; TBAJ 587; TBAJ587 |
| 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 | Anti-tuberculosis |
| ln Vitro | Bedaquiline belongs to the diarylquinoline class of drugs that have demonstrated clinical effectiveness in treating drug-resistant tuberculosis. However, because of its strong inhibition of the cardiac potassium channel protein hERG, bedaquiline has the potential to cause cardiac problems. An analogue of bedaquiline, TBAJ-587, exhibits significantly lessened hERG blockade and more powerful anti-tubercular action. TBAJ-587 has an IC50 of 13 μM for inhibiting the hERG channel[1]. |
| References | 3,5-Dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel. Bioorg Med Chem. 2019 Apr 1;27(7):1292-1307. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~43.33 mg/mL (~70.51 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (3.53 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 21.7 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: ≥ 2.17 mg/mL (3.53 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 21.7 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: ≥ 2.17 mg/mL (3.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 21.7 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: ≥ 2.17 mg/mL (3.53 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6273 mL | 8.1367 mL | 16.2734 mL | |
| 5 mM | 0.3255 mL | 1.6273 mL | 3.2547 mL | |
| 10 mM | 0.1627 mL | 0.8137 mL | 1.6273 mL |