눈에 묻으면 몇 분간 물로 조심해서 씻으시오. 가능하면 콘택트렌즈를 제거하시오. 계속 씻으시오.
P330
입을 씻어내시오.
P332+P313
피부 자극이 생기면 의학적인 조치· 조언을 구하시오.
P337+P313
눈에 대한 자극이 지속되면 의학적인 조치· 조언를 구하시오.
P362
오염된 의복을 벗고 세척 후에 재사용하기
P403+P233
용기는 환기가 잘 되는 곳에 단단히 밀폐하여 저장하시오.
P405
밀봉하여 저장하시오.
P501
...에 내용물 / 용기를 폐기 하시오.
Bedaquiline fumarate C화학적 특성, 용도, 생산
개요
Bedaquiline fumarate (BQF) is an FDA-approved antituberculosis drug that targets the enzyme ATP synthase. It is a fumarate salt prepared from equimolar amounts of bedaquiline and fumaric acid. It can be used in combination therapy for the treatment of multidrug-resistant tuberculosis in the lungs of adults (18 years of age and older). The new BQF microemulsion dosage form of BQF has improved oral bioavailability over the previous formulation, and the BQF microemulsion is cytocompatible with significantly higher cellular uptake than the control group at the highest concentration of 500 μg/ml, which could lead to further use in the effective treatment of multidrug-resistant tuberculosis[1].
정의
ChEBI: Bedaquiline fumarate is a fumarate salt prepared from equimolar amounts of bedaquiline and fumaric acid. It is used in combination therapy 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 contains a bedaquiline(2+).
Clinical Use
Bedaquiline fumarate is a diarylquinone drug developed by Janssen Pharmaceutical which is
marketed under the trade name Sirturo ®. The drug, which was approved in 2012 for the treatment of
multidrug-resistant tuberculosis (MDR-TB), was developed in partnership with Johnson & Johnson and
represents the first new tuberculosis therapy approved in over four decades. Bedaquiline is the first
member of a new class of diarylquinone compounds whose mechanism of action inhibits Mycobaterium
tuberculosis ATP synthase which deprives bacterium of energy.
Synthesis
Of the relatively few synthetic approaches to bedaquiline (or its fumarate salt) that have been
reported, the most likely process-scale route is that described by Porstmann and co-workers from
Janssen Pharmaceutical, and this route is outlined in the scheme. The synthesis was initiated by first
freebasing commercially available dimethylaminoketone 31 with sodium hydroxide to provide naphthylone 32 in nearly quantitative yield. Subjection of commercially available quinoline 33 to LDA
removed the benzyllic proton within this system and subsequent trap with naphthylone 32 gave rise to a
mixture of diastereomers whereby the major diastereomer obtained from this reaction corresponded to
the bedaquiline geometry. The minor diastereomer was resolved through multiple recrystallizations and
seeding techniques. This racemate of the major diastereomer subsequently underwent a chiral
resolution upon treatment with BINAP derivative 34 in refluxing DMSO and then upon cooling and
subjection to aqueous base in warm toluene furnished bedaquiline 35 bearing the requisite (R,S)-
configuration of the two vicinal chiral centers corresponding to that of the drug. The overall yield of the
conversion of 33 to enantiopure 35 was 39%. Aminoquinolinol 35 was then prepared as the
corresponding fumarate salt upon treatment with fumaric acid in the presence of isopropanol, and this
salt formation delivered bedaquiline fumarate (VI) in 82% yield.
