NAMES AND DATABASE IDS
NAMES AND DATABASE IDS
Names Database IDs
IUPAC name
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2-{2-methyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl}-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one
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IUPAC Traditional name
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2-{2-methyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl}-8-nitro-6-(trifluoromethyl)-1,3-benzothiazin-4-one
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Synonyms
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BTZ038
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BTZ044
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BTZ043 racemate
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CAS Number
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PubChem SID
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PubChem CID
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DATA SOURCES
DATA SOURCES
All Sources Commercial Sources Non-commercial Sources
CALCULATED PROPERTIES
CALCULATED PROPERTIES
JChem
H Acceptors
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7
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H Donor
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0
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LogD (pH = 5.5)
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3.6465611
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LogD (pH = 7.4)
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3.6465611
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Log P
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3.6465611
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Molar Refractivity
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98.1523 cm3
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Polarizability
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36.224674 Å3
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Polar Surface Area
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96.95 Å2
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Rotatable Bonds
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3
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Lipinski's Rule of Five
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true
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PROPERTIES
PROPERTIES
Safety Information
Product Information
Bioassay(PubChem)
Storage Condition
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-20°C
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Show
data source
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Salt Data
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racemate
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Show
data source
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DETAILS
DETAILS
Selleck Chemicals
Selleck Chemicals -
S1097
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Research Area
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Description
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Infection |
Biological Activity
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Description
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BTZ043 racemate is a decaprenylphosphoryl-β-D-ribose 2’-epimerase inhibitor acting as a new antimycobacterial agent that kill Mycobacterium tuberculosis. |
Targets
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Decaprenylphosphoryl-β-D-ribose 2’-epim |
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IC50 |
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In Vitro
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By targeting decaprenylphosphoryl-β-D-ribose 2’-epimerase, BTZ043 abolishes the formation of decaprenylphosphoryl arabinose, leading to cell lysis and death of Mycobacterium tuberculosis. BTZ043 displays similar activity against all clinical isolates of M. tuberculosis, including multidrug-resistant and extensively drug-resistant strains. BTZ043 displays significant activity against M. tuberculosis H37Rv and Mycobacterium smegmatis with MIC of 1 ng/mL (2.3 nM) and 4 ng/mL (9.2 nM), respectively, which is more potent than those of the existing tuberculosis (TB) drugs isoniazid (INH) and ethambutol (EMB) with MIC of 0.02-0.2 μg/mL and 1-5 μg/mL, respectively. BTZ043 is less effective in two different model systems (auxotrophy and starvation) involving metabolically inert M. tuberculosis, indicating that BTZ043 blocks a step in active metabolism similar to isoniazid (INH). BTZ043 treatment in M. smegmatis cells decreases the growth rate rapidly followed by a swelling of the poles and lysis of the cells after a few hours, which is similar but delayed in M. tuberculosis. [1] BTZ043 (1/4 MIC 0.375 ng/mL) in combination with TMC207 (1/4 MIC 20 ng/mL) has a stronger cidal effect on M. tuberculosis but not BTZ-resistant M. tuberculosis mutant than TMC207 alone at a concentration of 80 ng/mL. [2] |
In Vivo
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In a mouse model of chronic tuberculosis, administration of BTZ043 at 37.5 mg/kg or 300 mg/kg for 4 weeks reduces the bacterial burden in the lungs and spleens by 1 and 2 logs, respectively. [1] |
Clinical Trials
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Features
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More active than EMB against M. tuberculosis. |
Protocol
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Animal Study
[1]
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Animal Models |
BALB/c mice infected with a low bacillary load (~200 CFU) of M. tuberculosis H37Rv via aerosol |
Formulation |
Formulated in carboxymethyl cellulose formulation (0.25%) |
Doses |
37.5 mg/kg, or 300 mg/kg |
Administration |
Oral gavage once daily |
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PATENTS
PATENTS
PubChem Patent
Google Patent