Details
Stereochemistry | ACHIRAL |
Molecular Formula | C20H23F3N4O3S |
Molecular Weight | 456.482 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[O-][N+](=O)C1=C2SC(=NC(=O)C2=CC(=C1)C(F)(F)F)N3CCN(CC4CCCCC4)CC3
InChI
InChIKey=BJDZBXGJNBMCAV-UHFFFAOYSA-N
InChI=1S/C20H23F3N4O3S/c21-20(22,23)14-10-15-17(16(11-14)27(29)30)31-19(24-18(15)28)26-8-6-25(7-9-26)12-13-4-2-1-3-5-13/h10-11,13H,1-9,12H2
Molecular Formula | C20H23F3N4O3S |
Molecular Weight | 456.482 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
2-[4-(CYCLOHEXYLMETHYL)-1-PIPERAZINYL]-8-NITRO-6-(TRIFLUOROMETHYL)-4H-1,3-BENZOTHIAZIN-4-ONE (Macozinone, PBTZ169) is a piperazinobenzothiazinone derivative optimized by medicinal chemistry from the lead BTZ043. Macozinone is a tuberculosis (TB) drug candidate that specifically targets the essential flavoenzyme DprE1, thereby blocking synthesis of the cell wall precursor decaprenyl phosphoarabinose (DPA) and provoking lysis of Mycobacterium tuberculosis. The company Nearmedic Plus leads PBTZ169 development for the Russian market and associated countries and has completed an open-labelled, dose-escalation phase I study in healthy male volunteers followed by a Multiple Ascending Dose in 2016. In 2017, a phase IIa EBA study (monotherapy during 14 days) was initiated in DS-TB patients in Russia and Belarus. It was completed in February 2018 with 16 patients enrolled. Nearmedic Plus indicated it confirmed the good safety in DS-TB patients and the statistically significant EBA after 14 days monotherapy in the group of 7 patients treated with 640 mg of PBTZ169. The EPFL-based non-profit Innovative Medicines for Tuberculosis (iM4TB) foundation (Lausanne, Switzerland) is leading PBTZ169 development in the rest of the world.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: P9WJF1 Gene ID: 886125.0 Gene Symbol: dprE1 Target Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25987616 |
PubMed
Title | Date | PubMed |
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Towards a new combination therapy for tuberculosis with next generation benzothiazinones. | 2014 Mar |
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In Vivo Activity of the Benzothiazinones PBTZ169 and BTZ043 against Nocardia brasiliensis. | 2015 |
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Structure-Based Drug Design and Characterization of Sulfonyl-Piperazine Benzothiazinone Inhibitors of DprE1 from Mycobacterium tuberculosis. | 2018 Oct |
Sample Use Guides
This last study investigated the safety, tolerability and pharmacokinetics of PBTZ169 at doses up to 640 mg once daily for 14 days and revealed a good safety profile of the drug.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26474057
In vitro activity of PBTZ169, was tested against thirty Nocardia brasiliensis isolates. The MIC50 and MIC90 values for PBTZ169 were 0.0075 and 0.03 ug/mL, respectively.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sun Dec 18 14:52:41 UTC 2022
by
admin
on
Sun Dec 18 14:52:41 UTC 2022
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Record UNII |
A3M1353L40
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Record Status |
Validated (UNII)
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1377239-83-2
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57331386
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10732
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A3M1353L40
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C174599
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DB14821
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TARGET ORGANISM->INHIBITOR |
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ACTIVE MOIETY |