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Details

Stereochemistry ACHIRAL
Molecular Formula C29H28ClF3N4O2
Molecular Weight 557.006
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TELACEBEC

SMILES

CCC1=C(N2C=C(Cl)C=CC2=N1)C(=O)NCC3=CC=C(C=C3)N4CCC(CC4)C5=CC=C(OC(F)(F)F)C=C5

InChI

InChIKey=OJICYBSWSZGRFB-UHFFFAOYSA-N
InChI=1S/C29H28ClF3N4O2/c1-2-25-27(37-18-22(30)7-12-26(37)35-25)28(38)34-17-19-3-8-23(9-4-19)36-15-13-21(14-16-36)20-5-10-24(11-6-20)39-29(31,32)33/h3-12,18,21H,2,13-17H2,1H3,(H,34,38)

HIDE SMILES / InChI
Molecular Formula C29H28ClF3N4O2
Molecular Weight 557.006
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Q203 (6-chloro-2-ethyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)imidazo [1,2-a]pyridine-3-carboxamide) is an an imidazopyridine antitubercular compound. Q203 targets the cytochrome b subunit (QcrB) of the cytochrome bc1 complex. This complex is an essential component of the respiratory electron transport chain of ATP synthesis. Q203 inhibited the growth of multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Q203 is a promising new clinical candidate for the treatment of tuberculosis.

Originator

Pethe, K. et al.
2

Approval Year

Unknown
149,124

Targets

Primary TargetPharmacologyConditionPotency
Ubiquinol-cytochrome c reductase cytochrome b subunit
2
Inhibitor
8,504

Conditions

ConditionModalityTargetsHighest PhaseProduct
Tuberculosis
83
 Curative
Phase I
438
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
1490 ng/mL
10 mg/kg single, oral
 Q-203 plasma
Mus musculus
0.92 μg/mL
10 mg/kg single, oral
 Q-203 plasma
Mus musculus

AUC

ValueDoseCo-administeredAnalytePopulation
44100 ng × h/mL
10 mg/kg single, oral
 Q-203 plasma
Mus musculus
23.91 μg × h/mL
10 mg/kg single, oral
 Q-203 plasma
Mus musculus

T1/2

ValueDoseCo-administeredAnalytePopulation
23.4 h
10 mg/kg single, oral
 Q-203 plasma
Mus musculus

Doses

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2,252

inducer
1,087
inhibitor
2,438
inhibitor
2,507
inhibitor
2,217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1,741

CYP1A2
2,153

CYP2C19
2,057
P-gp
2,052

HLM
34

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

20130065884
2
20140155387
2
8865734
2
9029389
2
WO2011113606A1
2
WO2012143796A2
2

Sample Use Guides

In Vivo Use Guide
The Phase I clinical trial (clinicaltrials.gov identifier: NCT02530710) enrolling healthy patients is a dose-escalation study starting at 100 mg dosing that will be adjusted based on PK analysis.
Route of Administration: Oral
In Vitro Use Guide
Q203 inhibited the growth of multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range
Substance Class Chemical
Record UNII
55G92WGH3X
Record Status Validated (UNII)
Record Version
NIH
NCATS
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