TBA-354   Click here for help

GtoPdb Ligand ID: 13546

Compound class: Synthetic organic
Comment: TBA-354 is a nitroimidazole-based antibacterial compound derived from pretomanid (PA-824) [1]. It has narrow-spectrum activity, inhibiting Mycobacterium tuberculosis and Mycobacterium bovis but not nontuberculous mycobacteria (NTM) or the Gram-positive and Gram-negative bacteria tested [2]. TBA-354 was under clinical development for the treatment of tuberculosis (TB), by the non-profit organisation TB Alliance (www.tballiance.org.za), but was discontinued in 2016 [3].

TBA-354 is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 0
Rotatable bonds 7
Topological polar surface area 98.79
Molecular weight 436.34
XLogP 2.35
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES C1=C(C=NC(=C1)C2=CC=C(C=C2)OC(F)(F)F)CO[C@H]3CN4C=C(N=C4OC3)[N+](=O)[O-]
Isomeric SMILES C1[C@@H](COC2=NC(=CN21)[N+](=O)[O-])OCC3=CN=C(C=C3)C4=CC=C(C=C4)OC(F)(F)F
InChI 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
InChI Key ZXSGSFMORAILEY-HNNXBMFYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Kmentova I, Sutherland HS, Palmer BD, Blaser A, Franzblau SG, Wan B, Wang Y, Ma Z, Denny WA, Thompson AM. (2010)
Synthesis and structure-activity relationships of aza- and diazabiphenyl analogues of the antitubercular drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824).
J Med Chem, 53 (23): 8421-39. [PMID:21069962]
2. Upton AM, Cho S, Yang TJ, Kim Y, Wang Y, Lu Y, Wang B, Xu J, Mdluli K, Ma Z et al.. (2015)
In vitro and in vivo activities of the nitroimidazole TBA-354 against Mycobacterium tuberculosis.
Antimicrob Agents Chemother, 59 (1): 136-44. [PMID:25331696]
3.  Phase 1 Clinical Trial of TB Drug Candidate TBA-354 Discontinued.
Accessed on 29/09/2024. Modified on 29/09/2024. TB Alliance, https://www.tballiance.org/news/phase-1-clinical-trial-tb-drug-candidate-tba-354-discontinued