ZA7371
ZA7371 Basic information
- Product Name:
- ZA7371
- Synonyms:
-
- N-(2-Hydroxyethyl)-1-[(6-methoxy-5-methylpyrimidin-4-yl)methyl]-6-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide
- ZA7371
- DprE1-IN-1
- AZ-7371
- AZ-7371(DprE1-IN-1)
- TBA-7371
- DprE1-IN-1 ZA7371
- AZ7371;AZ 7371
- CAS:
- 1494675-86-3
- MF:
- C18H21N5O3
- MW:
- 355.39
- Mol File:
- 1494675-86-3.mol
ZA7371 Chemical Properties
- Boiling point:
- 691.6±55.0 °C(Predicted)
- Density
- 1.34±0.1 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- DMSO : 11 mg/mL (30.95 mM)
- pka
- 12.79±0.46(Predicted)
- form
- A crystalline solid
- color
- White to off-white
ZA7371 Usage And Synthesis
Uses
TBA-7371 is an orally active and non-covalent inhibitor of Decaprenylphosphoryl-β-D-ribose oxidase (DprE1) of Mycobacterium tuberculosis (MIC=0.64 μg/mL). TBA-7371 can block the synthesis of arabinose in the bacterial cell wall, resulting in cell wall structural defects, thereby exerting an anti-tuberculosis effect. TBA-7371 can be used in the research of anti-tuberculosis drugs and has a synergistic bactericidal effect with Bedaquiline (HY-14881) and other drugs[1][2][3].
in vivo
TBA-7371 (100, 200 mg/kg; oral gavage; twice daily; 4-8 weeks) synergistically exerts bactericidal and fungicidal activity with Bedaquiline (HY-14881) and GSK2556286 (HY-147017) in the BALB/c mouse tuberculosis model[3].
TBA-7371 (50, 100, 200 mg/kg; oral gavage; twice daily; 8 weeks) significantly reduces bacterial burden in lung tissue after 8 weeks of treatment in the C3HeB/Fe J mouse tuberculosis model[3].
| Animal Model: | Female BALB/c mice (5-6 weeks old, specific pathogen-free) + subacute tuberculosis infection model induced by aerosol of *Mycobacterium tuberculosis* H37Rv[3] |
| Dosage: | 100 mg/kg, 200 mg/kg (0.5% carboxymethylcellulose + 0.1% Tween 80) |
| Administration: | Oral gavage, twice daily (8 h apart), 5 days/week for 4-8 weeks; Combination with Bedaquiline (25 mg/kg) and GSK2556286 (50 mg/kg) (BGA regimen) |
| Result: | At 100 or 200 mg/kg bid significantly increased bactericidal activity after 8 weeks, with lung CFU counts of 1.48 (200 mg/kg) and 1.78 (100 mg/kg), demonstrating superior sterilizing activity compared to two-drug combinations. |
| Animal Model: | Female C3HeB/FeJ mice (8-10 weeks old, specific pathogen-free) + chronic tuberculosis infection model with caseous necrotic pulmonary lesions induced by aerosol of *Mycobacterium tuberculosis* Erdman[3] |
| Dosage: | 50 mg/kg, 100 mg/kg, 200 mg/kg (0.5% carboxymethylcellulose + 0.1% Tween 80) |
| Administration: | Oral gavage, twice daily, 5 days/week for 8 weeks |
| Result: | After 8 weeks, all dose groups showed significant reduction in lung bacterial burden compared to untreated controls. The 100 and 200 mg/kg groups achieved approximately 1.5 log CFU reduction, with dose-dependent efficacy. At 100 mg/kg bid exhibited consistent bactericidal activity, with higher drug retention in caseous lesions at trough concentrations. |
References
[1] Gawad J, et al. Decaprenyl-phosphoryl-ribose 2'-epimerase (DprE1): challenging target for antitubercular drug discovery. Chem Cent J. 2018 Jun 23;12(1):72. DOI:10.1186/s13065-018-0441-2
[2] Robertson GT, et al. Comparative Analysis of Pharmacodynamics in the C3HeB/FeJ Mouse Tuberculosis Model for DprE1 Inhibitors TBA-7371, PBTZ169, and OPC-167832. Antimicrob Agents Chemother. 2021 Oct 18;65(11):e0058321. DOI:10.1128/AAC.00583-21
[3] Li S-Y, et al. Bactericidal and sterilizing activity of novel regimens combining bedaquiline or TBAJ-587 with GSK2556286 and TBA-7371 in a mouse model of tuberculosis. Antimicrob Agents Chemother. 2024 Apr 3;68(4):e0156223. DOI:10.1128/aac.01562-23
ZA7371Supplier
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- sales@boylechem.com
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- 021-58950125
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- 021-58955995
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- info@yuhaochemical.com
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- 021-52996696，15000506266 15000506266