TBA-354

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H15F3N4O5
Molecular Weight	436.3414
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

[O-][N+](=O)C1=CN2C[C@@H](COC2=N1)OCC3=CC=C(N=C3)C4=CC=C(OC(F)(F)F)C=C4

InChI

InChIKey=ZXSGSFMORAILEY-HNNXBMFYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C19H15F3N4O5
Molecular Weight	436.3414
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

TBA-354, also 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. TBA-354 emerged from studies designed to identify a next generation nitroimidazole for TB. TB Alliance conducted the studies in collaboration with the University of Auckland and University of Illinois-Chicago. Once identified, TB Alliance further advanced TBA-354 through pre-clinical development and is now the sponsor of the Phase 1 study.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mycobacterium tuberculosis H37Rv 11	Inhibitor 8,297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tuberculosis 83	Curative		Phase I 428	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2049 ng/mL	20 mg/kg single, intraperitoneal		TBA-354 plasma	Rattus norvegicus

AUC

Value	Dose	Co-administered	Analyte	Population
10135 ng × h/mL	20 mg/kg single, intraperitoneal		TBA-354 plasma	Rattus norvegicus

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.24 h	20 mg/kg single, intraperitoneal		TBA-354 plasma	Rattus norvegicus

F_unbound

Value	Dose	Co-administered	Analyte	Population
3.5%	unknown, unknown		TBA-354 plasma	Homo sapiens

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P000P1Z	https://www.1pchem.com/search?query=1P000P1Z
Angene	AGN-PC-0WCSMZ	http://www.angenechemical.com/productshow/AGN-PC-0WCSMZ.html
ApexBio Technology	B5935	https://www.apexbt.com/catalogsearch/result/?q=B5935
AstaTech	40893	http://astatechinc.com/CPSResult.php?CRNO=40893
BLD Pharm	BD304696	http://www.bldpharm.com/search/Search.html?keyword=BD304696

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PubMed

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Title	Date	PubMed
In vitro and in vivo activities of the nitroimidazole TBA-354 against Mycobacterium tuberculosis.	2015 Jan	25331696
Contribution of the nitroimidazoles PA-824 and TBA-354 to the activity of novel regimens in murine models of tuberculosis.	2015 Jan	25331697

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Patents

Sample Use Guides

In Vivo Use Guide

10-1000 mg TBA-354 supplied as a 20 mg /mL suspension and matching placebo suspension for oral administration.

Route of Administration: Oral

In Vitro Use Guide

The MIC range for TBA-354 across the 10 M. tuberculosis strains tested was <0.02 to 0.36 uM.

Substance Class	Chemical
Record UNII	911T37M2WY
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

TBA-354

Common Name

English

TBA 354

Code

English

(SN31354((S)-2-NITRO-6-((6-(4-TRIFLUOROMETHOXY)PHENYL)PYRIDINE-3-YL)METHOXY)-6,7-DIHYDRO-5H-IMIDAZO(2,1-B)(1,3)OXAZINE))

Systematic Name

English

((6S)-6-((6-(4-(TRIFLUOROMETHOXY)PHENYL)-3-PYRIDYL)METHOXY)-6,7-DIHYDRO-5H-IMIDAZO(2,1-B)(1,3)OXAZIN-2-YL)AZINIC ACID

Systematic Name

English

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Code System

Code

Type

Description

PUBCHEM

49836057

PRIMARY

CAS

1403987-02-9

NO STRUCTURE GIVEN

FDA UNII

911T37M2WY

PRIMARY

CAS

1257426-19-9

PRIMARY

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Related Record

Type

Details


					R0EM8D5HFD

MYCOBACTERIUM TUBERCULOSIS

TARGET ORGANISM->INHIBITOR

Qualification:

MIC

Amount:

6 NANOMOLAR (average)

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Related Record

Type

Details


					911T37M2WY

TBA-354

ACTIVE MOIETY

Comments:

Official Title: A Phase I, Double-Blind, Placebo Controlled, Randomized, Multiple Ascending Dose Study With a Dose Formulation Comparison Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBA-354 in Healthy Adult Subjects Purpose: The objective of the study is to evaluate the safety and tolerability of multiple doses of TBA-354 in healthy subjects.


					911T37M2WY

TBA-354

ACTIVE MOIETY

Comments:

TBA-354 MICs and MBCs against M. tuberculosis H37Rv: MIC (replicating) = 0.006 .MU.M, MBC (replicating) = 0.006 .MU.M, LORA (NR) MIC = 0.27 .MU.M, LORA (NR) MBC = 3.4 .MU.M, 4% BSAb MIC (replicating) = 0.011 .MU.M, 10% FBSc MIC (replicating) = 0.012 .MU.M


					911T37M2WY

TBA-354

ACTIVE MOIETY

Comments:

Originator: Global Alliance for TB Drug Development, University of Auckland; Developer: Global Alliance for TB Drug Development; Class: Antitubercular, Nitroimidazole, Oxazine, Pyridine, Small molecule; Mechanism of Action: Undefined mechanism; Orphan Drug Status: No; On Fast track: No; New Molecular Entity: Yes; Highest Development Phase: Phase I for Tuberculosis; Most Recent Events: 19 Nov 2015 Global Alliance for TB Drug Development plans a phase I trial in Healthy volunteers in USA (NCT02606214), 01 Jan 2015 Phase-I clinical trials in Tuberculosis (In volunteers) in USA (PO), 12 Sep 2012 Pharmacodynamics & pharmacokinetics data from preclinical studies in Tuberculosis presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2012)

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SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound