2-{2-methyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl}-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one

• ChemBase ID: 72512
• Molecular Formular: C17H16F3N3O5S
• Molecular Mass: 431.3862496
• Monoisotopic Mass: 431.07627629
• SMILES: c1(cc(c2c(c1)c(=O)nc(s2)N1CCC2(CC1)OCC(O2)C)[N+](=O)[O-])C(F)(F)F
• Canonical SMILES: CC1COC2(O1)CCN(CC2)c1nc(=O)c2c(s1)c(cc(c2)C(F)(F)F)[N+](=O)[O-]
• InChI: InChI=1S/C17H16F3N3O5S/c1-9-8-27-16(28-9)2-4-22(5-3-16)15-21-14(24)11-6-10(17(18,19)20)7-12(23(25)26)13(11)29-15/h6-7,9H,2-5,8H2,1H3
• InChIKey: GTUIRORNXIOHQR-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-{2-methyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl}-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one
• IUPAC Traditional name: 2-{2-methyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl}-8-nitro-6-(trifluoromethyl)-1,3-benzothiazin-4-one
• Synonyms: BTZ038; BTZ044; BTZ043 racemate

Database IDs

• CAS Number: 1161233-85-7
• PubChem SID: 162037437
• PubChem CID: 49769085

CALCULATED PROPERTIES

• H Acceptors: 7
• H Donor: 0
• LogD (pH = 5.5): 3.6465611
• LogD (pH = 7.4): 3.6465611
• Log P: 3.6465611
• Molar Refractivity: 98.1523 cm^3
• Polarizability: 36.224674 Å^3
• Polar Surface Area: 96.95 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Product Information

• Salt Data: racemate

DETAILS

Selleck Chemicals - S1097

Research Area

• Description: Infection

Biological Activity

• Description: BTZ043 racemate is a decaprenylphosphoryl-β-_D-ribose 2’-epimerase inhibitor acting as a new antimycobacterial agent that kill Mycobacterium tuberculosis.
• Targets: Decaprenylphosphoryl-β-_D-ribose 2’-epim
• In Vitro: 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: 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]
• Features: More active than EMB against M. tuberculosis.

Protocol

• Protocol: Animal Study ^[1]
• 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

References

• References: [1] Makarov V, et al. Science, 2009, 324(5928), 801-804.
• References: [2] Lechartier B, et al. Antimicrob Agents Chemother, 2012.

REFERENCES

• Makarov V, et al. Science, 2009, 324(5928), 801-804.
• Lechartier B, et al. Antimicrob Agents Chemother, 2012.