TBA-354, formerly known as SN31354, is a potent anti-tuberculosis drug candidate. TBA-354 is narrow spectrum and bactericidal in vitro against replicating and nonreplicating Mycobacterium tuberculosis, with potency similar to that of delamanid and greater than that of PA-824. TBA-354 maintains activity against Mycobacterium tuberculosis H37Rv isogenic monoresistant strains and clinical drug-sensitive and drug-resistant isolates. TBA-354 is a promising next-generation nitroimidazole antitubercular agent.

Physicochemical Properties

Molecular Formula	C19H15F3N4O5
Molecular Weight	436.341414690018
Exact Mass	436.099
Elemental Analysis	C, 52.30; H, 3.47; F, 13.06; N, 12.84; O, 18.33
CAS #	1257426-19-9
Related CAS #	1257426-19-9;
PubChem CID	49836057
Appearance	Solid powder
Density	1.5±0.1 g/cm3
Boiling Point	570.0±60.0 °C at 760 mmHg
Flash Point	298.5±32.9 °C
Vapour Pressure	0.0±1.6 mmHg at 25°C
Index of Refraction	1.623
LogP	3.02
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	5
Heavy Atom Count	31
Complexity	614
Defined Atom Stereocenter Count	1
SMILES	FC(F)(F)OC1=CC=C(C2=CC=C(CO[C@H]3CN4C(OC3)=NC([N+]([O-])=O)=C4)C=N2)C=C1
InChi Key	ZXSGSFMORAILEY-HNNXBMFYSA-N
InChi Code	InChI=1S/C19H15F3N4O5/c20-19(21,22)31-14-4-2-13(3-5-14)16-6-1-12(7-23-16)10-29-15-8-25-9-17(26(27)28)24-18(25)30-11-15/h1-7,9,15H,8,10-11H2/t15-/m0/s1
Chemical Name	(S)-2-nitro-6-((6-(4-(trifluoromethoxy)phenyl)pyridin-3-yl)methoxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
Synonyms	TBA-354; TBA 354; TBA354; SN31354; SN-31354; SN 31354
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

References

[1]. In Vitro and In Vivo Activities of the Nitroimidazole TBA-354 against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015 Jan;59(1):136-44. [2]. Contribution of the Nitroimidazoles PA-824 and TBA-354 to the Activity of Novel Regimens in Murine Models of Tuberculosis. Antimicrob Agents Chemother. 2015 Jan;59(1):129-35.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~229.18 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.73 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.73 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 2.5 mg/mL (5.73 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: 2.5 mg/mL (5.73 mM)  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2918 mL	11.4590 mL	22.9179 mL
	5 mM	0.4584 mL	2.2918 mL	4.5836 mL
	10 mM	0.2292 mL	1.1459 mL	2.2918 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.