957217-65-1

Basic information

• Product Name: BTZ043 (BTZ038, BTZ044)
• Synonyms: BTZ043 (BTZ038, BTZ044);4H-1,3-Benzothiazin-4-one, 2-(2-methyl-1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-8-nitro-6-(trifluoromethyl)-;2-(3-methyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-8-nitro-6-(trifluoromethyl)-1,3-benzothiazin-4-one BTZ043 Racemate;Benzothiazinone 10526038;BTZ 10526038;2-(2-Methyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-8-nitro-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-4-one
• CAS NO: 957217-65-1
• Molecular Formula: C17H16F3N3O5S
• Molecular Weight: 431.3862496
• EINECS: 604-604-1
• Product Categories: Inhibitors
• Mol File: 957217-65-1.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 547.6±60.0 °C(Predicted)
• Appearance: /
• Density: 1.68±0.1 g/cm3(Predicted)
• Solubility: insoluble in H2O; ≥10.4 mg/mL in DMSO with gentle warming; ≥3.27 mg/mL in EtOH with gentle warming and ultrasonic
• PKA: -0.51±0.20(Predicted)
• CAS DataBase Reference: BTZ043 (BTZ038, BTZ044)(CAS DataBase Reference)
• NIST Chemistry Reference: BTZ043 (BTZ038, BTZ044)(957217-65-1)
• EPA Substance Registry System: BTZ043 (BTZ038, BTZ044)(957217-65-1)

Safety Data

• Hazardous Substances Data: 957217-65-1(Hazardous Substances Data)

Usage

Biological Activity

mic: 1 ng/ml (2.3 nm) for m. tuberculosis h37rv and 4 ng/ml (9.2 nm) for mycobacterium smegmatisthe loss of human lives to tuberculosis (tb) continues unabated as a result of poverty, synergy with the hiv/aids pandemic, and the emergence of multidrug- and extensively drug-resistant strains of mycobacterium tuberculosis. btz043 is the most advanced candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant tb.

in vitro

btz043 displayed similar activity against all clinical isolates of m. tuberculosis that were tested, including extensively drug-resistant and multidrug-resistant strains, indicating that it targets a previously unknown biological function. btz043 is bactericidal, reducing viability in vitro by more than 1000-fold in under 72 hours, which is comparable to the inh killing effect [1].

in vivo

the in vivo efficacy of btz043 was assessed 4 weeks after a low-dose aerosol infection of in the chronic balb/c mice model of tb. four weeks of treatment with btz043 reduced the bacterial load in the lungs and spleens by 1 and 2 logs, respectively, at the concentrations used. additional findings suggest that btz efficacy is time- rather than dose-dependent [1].

references

[1] makarov v, manina g, mikusova k, et al. benzothiazinones kill mycobacterium tuberculosis by blocking arabinan synthesis. science. 2009 may 8;324(5928):801-4.

Upstream product

• 22227-59-4 2-chloro-3-nitro-5-(trifluoromethyl)benzoic acid 
• 17402-25-4 2-methyl-1,4-dioxa-8-azaspiro[4.5]-decane 
• 1449698-48-9 2-chloro-3-nitro-5-(trifluoromethyl)benzoyl isothiocyanate 
• 40064-34-4 piperidine-4,4-diol hydrochloride 
• 22227-47-0 2-chloro-3-nitro-5-(trifluoromethyl)benzamide 
• 1344087-80-4 (S)-2-methyl-1,4-dioxa-8-azaspiro[4.5]decane 
• 1344087-73-5 2‐(methylthio)‐8‐nitro‐6‐(trifluoromethyl)‐1,3‐ benzothiazin‐4‐one 
• 140-89-6 potassium ethyl xanthogenate 
• 4254-15-3 (S)-1,2-Propanediol 
• 1396842-55-9 8-nitro-2-(4-oxopiperidin-1-yl)-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-4-one 
• 41661-47-6 piperidin-4-one 
• 87033-30-5 2-chloro-3-nitro-5-(trifluoromethyl)benzoyl chloride 

Relevant articles and documents

Efficient Synthesis of Benzothiazinone Analogues with Activity against Intracellular Mycobacterium tuberculosis

8-Nitrobenzothiazinones (BTZs) are a promising class of antimycobacterial agents currently under investigation in clinical trials. Starting from thiourea derivatives, a new synthetic pathway to BTZs was established. It allows the formation of the thiazinone ring system in one synthetic step and is applicable for preparation of a wide variety of BTZ analogues. The synthetic procedure furthermore facilitates the replacement of the sulphur atom in the thiazinone ring system by oxygen or nitrogen to afford the analogous benzoxazinone and quinazolinone systems. 36 BTZ analogues were prepared and tested in luminescence-based assays for in vitro activity against Mycobacterium tuberculosis (Mtb) using the microdilution broth method and a high-throughput macrophage infection assay.

Identification of antitubercular benzothiazinone compounds by ligand-based design

1,3-Benzothiazin-4-ones (BTZs) are a novel class of TB drug candidates with potent activity against M. tuberculosis. An in silico ligand-based model based on structure-activity data from 170 BTZ compounds was used to design a new series. Compounds were tested against a panel of mycobacterial strains and were profiled for cytotoxicity, stability, and antiproliferative effects. Several of the compounds showed improved activity against MDR-TB while retaining low toxicity with higher microsomal, metabolic, and plasma stability.

PROCESS FOR THE PREPARATION OF 2-AMINO-SUBSTITUTED 1,3-BENZOTHIAZINE-4-ONES

A process for preparing 2-aminosubstituted 1, 3 -benzothiazine- 4 -ones is provided which comprises the following step: Formula (I) wherein Y is halogen; R is independently selected from C1-6-alkyl which may optionally be substituted by halogen, -NO2, halogen, -CHO -COOR4 (wherein R4 is hydrogen or C1-6-alkyl) and -CN; R3 is C1-6-alkyl which may be substituted by halogen; X is halogen; and n is 0 or an integer of 1 to 4; if n is 2, 3 or 4, multiple Rs may be the same or different.