TMC-207

Bezeichnung:TMC-207

CAS-Nr843663-66-1

Englisch Name:TMC-207

CBNumberCB12473722

SummenformelC32H31BrN2O2

Molgewicht555.5

MOL-Datei843663-66-1.mol

TMC-207 physikalisch-chemischer Eigenschaften

Schmelzpunkt	104 °C
Siedepunkt	702.7±60.0 °C(Predicted)
Dichte	1.322±0.06 g/cm3(Predicted)
storage temp.	Room temperature
Löslichkeit	Soluble in DMSO (10 mg/ml)
Aggregatzustand	solid
pka	13.05±0.29(Predicted)
Farbe	White
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
CAS Datenbank	843663-66-1

Sicherheit

HS Code	2933499090
Giftige Stoffe Daten	843663-66-1(Hazardous Substances Data)

Gefahreninformationscode (GHS)

TMC-207 Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
In December 2012, the US FDA approved bedaquiline as part of combination therapy for the treatment of multi-drug resistant tuberculosis (MDRTB). Bedaquiline is the first drug approved for MDR-TB and is the first approval from a new class of antituberculosis agents in the past 40 years. Due to the high unmetmedical need for treating MDR-TB, the FDA granted bedaquiline accelerated approval based on Phase II results, providing patients access to the drug while additional clinical studies are carried out. Bedaquiline (also known as TMC207 and R207910) is a diarylquinoline that was discovered from a high-throughput, whole-cell screening strategy with Mycobacterium smegmatis used as a surrogate for M. tuberculosis. Bedaquiline is a single enantiomer of an initial screening hit. Bedaquiline has potent and selective activity against mycobacteria, and is active against both drug-sensitive and drug-resistant M. tuberculosis. The mechanism of action of bedaquiline is unique amongst anti-TB drugs and involves inhibition of mycobacterial ATP synthase; it is not active against human ATP synthase. Bedaquiline has in vivo activity in numerous preclinical models of TB infection, alone and in combination with other anti-TB agents, and has bactericidal activity in established TB infection models. Bedaquiline is synthesized in five steps from 3-phenylpropionic acid and para-bromoaniline. Following amide formation, treatment with POCl₃ and DMF under Vilsmeier–Hack conditions gave a 2-chloroquinoline product. Treatment with sodium methoxide, followed by condensation with 3-(dimethylamino)-1-(naphthalen-1-yl)propan-1-one, and separation of isomers gave bedaquiline.
Beschreibung
TMC207 is a diarylquinoline that selectively inhibits the proton pump of the mycobacterial ATP synthase. It demonstrates potent activity against both drug-sensitive and drug-resistant M. tuberculosis and other mycobacterial species with MIC₅₀ values of ~0.03 μg/ml.
Originator
Janssen (Belgium)
Verwenden
Labeled Bedaquiline, intended for use as an internal standard for the quantification of Bedaquiline by GC- or LC-mass spectrometry.
Verwenden
(αS,βR)-Bedaquiline is a diarylquinoline derivative that acts as a mycobacterial inhibitor. Bedaquiline shows promise as potential drug in the treatment of tuberculosis.
Definition
ChEBI: Bedaquiline is a quinoline-based antimycobacterial drug used (as its fumarate salt) for the treatment of pulmonary multi-drug resistant tuberculosis by inhibition of ATP synthase, an enzyme essential for the replication of the mycobacteria. It has a role as an antitubercular agent and an ATP synthase inhibitor. It is a member of quinolines, a member of naphthalenes, an organobromine compound, an aromatic ether, a tertiary alcohol and a tertiary amino compound. It is a conjugate base of a bedaquiline(2+).
Trademarks
Sirturo
Einzelnachweise
Andries et al. (2005), A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis; Science, 307 223 Koul et al. (2007), Diarylquinolines target subunit c of mycobacterial ATP synthase; Nat. Chem. Biol., 3 323 Biukovic et al. (2013), Variations of subunit {varepsilon} of the Mycobacterium tuberculosis F1F0 ATP synthase and a novel model for mechanism of action of the tuberculosis drug TMC207; Antimicrob. Agents Chemother., 57 168 Sarathy et al. (2019), Re-Understanding the Mechanisms of Action of the Anti-Mycobacterial Drug Bedaquiline; Antibiotics (Basel), 8 261 Ghahremanpour et al. (2020), Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2; ACS Med. Chem. Lett., 11 2526

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