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| 化学名: | ベダキリン | | 英語化学名: | TMC-207 | | 别名: | TMC-207;R 207910;Bedaquiline(R 207910,TMC 207);Bedaquiline (TMC-207);(αS,βR)-Bedaquiline;bedaquinline;(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(methylamino)-2-(naphthalen-1-yl)-1-phenylbutan-2-ol;Bedaquiline D6 | | CAS番号: | 843663-66-1 | | 分子式: | C32H31BrN2O2 | | 分子量: | 555.5 | | EINECS: | 1308068-626-2 | | カテゴリ情報: | Inhibitors;API | | Mol File: | 843663-66-1.mol |  |
| 融点 | 104 °C | | 沸点 | 702.7±60.0 °C(Predicted) | | 比重(密度) | 1.322±0.06 g/cm3(Predicted) | | 貯蔵温度 | Room temperature | | 溶解性 | Soluble in DMSO (10 mg/ml) | | 外見 | solid | | 酸解離定数(Pka) | 13.05±0.29(Predicted) | | 色 | White | | 安定性： | 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 データベース | 843663-66-1 |
| | ベダキリン Usage And Synthesis |
| 効能 | 抗結核薬, ATP合成酵素阻害薬 | | 説明 | 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. | | 説明 | 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) | | 使用 | Labeled Bedaquiline, intended for use as an internal standard for the quantification of Bedaquiline by GC- or LC-mass spectrometry. | | 使用 | (αS,βR)-Bedaquiline is a diarylquinoline derivative that acts as a mycobacterial inhibitor. Bedaquiline shows promise as potential drug in the treatment of tuberculosis. | | 定義 | 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+). | | brand name | Sirturo | | 参考文献 | 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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