Ataluren
Ataluren атрибут
Температура плавления: |
241 - 242°C |
Температура кипения: |
503.7±60.0 °C(Predicted) |
плотность: |
1.379 |
температура хранения: |
Refrigerator |
растворимость: |
ДМСО (немного) |
форма: |
Твердое вещество от белого до почти белого цвета. |
пка: |
3.58±0.10(Predicted) |
цвет: |
От белого до не совсем белого |
InChI: |
InChI=1S/C15H9FN2O3/c16-12-7-2-1-6-11(12)14-17-13(18-21-14)9-4-3-5-10(8-9)15(19)20/h1-8H,(H,19,20) |
ИнЧИКей: |
OOUGLTULBSNHNF-UHFFFAOYSA-N |
SMILES: |
C(O)(=O)C1=CC=CC(C2N=C(C3=CC=CC=C3F)ON=2)=C1 |
Справочник по базе данных CAS: |
775304-57-9 |
FDA UNII: |
K16AME9I3V |
Код УВД: |
M09AX03 |
безопасность
- Заявления о рисках и безопасности
- код информации об опасности(GHS)
символ(GHS) |
|
сигнальное слово |
Warning |
Заявление об опасности |
пароль |
Заявление об опасности |
Класс опасности |
категория |
сигнальное слово |
пиктограмма |
предупреждение |
H336 |
Может вызывать сонливость или головокружение. |
Специфическая органная токсичность при однократном воздействии; Наркотические эффекты |
Категория 3 |
Предупреждение |
|
P261, P271, P304+P340, P312,P403+P233, P405, P501 |
H373 |
Может поражать органы (Нервная система) в результате
многократного или продолжительного воздействия при
вдыхании. |
Специфическая органная токсичность, многократное воздействие |
Категория 2 |
Предупреждение |
|
P260, P314, P501 |
|
Внимание |
P260 |
Не вдыхать газ/ пары/ пыль/ аэрозоли/ дым/ туман. |
P271 |
Использовать только на открытом воздухе или в хорошо
вентилируемом помещении. |
P304+P340+P312 |
ПРИ ВДЫХАНИИ: Свежий воздух, покой. Обратиться за
медицинской помощью при плохом самочувствии. |
P314 |
В случае плохого самочувствия обратиться к врачу. |
P403+P233 |
Хранить в хорошо вентилируемом месте в плотно
закрытой/герметичной таре. |
P405 |
Хранить в недоступном для посторонних месте. |
|
Ataluren химические свойства, назначение, производство
Описание
Ataluren is a drug marketed under the trade name Translarna®
which was developed by PTC Therapeutics and approved by the
European Union in May 2014 for the treatment of Duchenne’s muscular
dystrophy (DMD) and potentially other genetic disorders.
Ataluren renders ribosomes less sensitive to premature stop or
‘read-through’ codons, which are thought to be beneficial in diseases
such as DMD and cystic fibrosis.
Использование
Nonsense mutations create a premature termination of mRNA translation and have been implicated in various genetic disorders, including muscular dystrophy and cystic fibrosis. PTC-124 is a nonaminoglycoside that has been reported to selectively induce ribosomes to read through premature nonsense stop signals on mRNA, thus allowing the production of full-length, functional proteins. In a mouse model of cystic fibrosis caused by nonsense mutations, PTC-124 treatment (60 mg/kg s.c. injection or 0.3-0.9 mg/ml orally) has been shown to restore cystic fibrosis transmembrane conductance regulator (CFTR) protein expression and function. The target activity of PTC-124 was initially evaluated by firefly luciferase reporter cell-based nonsense codon assay (IC50 = 7 nM); however, subsequent assessments using a Renilla reniformis luciferase reporter have failed to produce nonsense codon suppression activity. Thus, while PTC-124 is in clinical testing in patients with nonsense mutations within the CFTR or dystrophin genes, controversy surrounds its exact mechanism of action.[Cayman Chemical]
Механизм действия
The mechanism of action of Ataluren (PTC124) is to generate functionally normal myotonic dystrophy proteins by facilitating ribosomal read-through of nonsense mutations, thereby bypassing the pathogenic variant and continuing the translation process. Under normal conditions, ribosomes move along the mRNA that links amino acids into proteins until they reach the stop codon. When the ribosome encounters a premature termination codon (PTC) due to a nonsense mutation, eukaryotic release factors [eRF1 (green) and eRF3 (turquoise) complexed with GTP (yellow)] are recruited, and translation is terminated prematurely to produce the truncated protein. Ataluren is thought to interact with the ribosome to promote the recruitment of the proximity-recognition tRNAs, which in turn inhibits the nonsense mutation, allowing the PTC to be read through and synthesised. PTC to be read through and synthesise full-length proteins. The red amino acid on the near-recognition tRNA is incorporated into the read-through protein product. In the Ataluren-mediated nonsense repression model, the X on the tRNA indicates a mispairing at codon position three.
Синтез
The sequence to construct ataluren, which was described by the
authors at PTC Therapeutics, commenced with commercially available
methyl 3-cyanobenzoate (38). This ester was exposed to
hydroxylamine in aqueous tert-butanol and warmed gently until
the reaction was deemed complete. Then this mixture was treated
with 2-fluorobenzoyl chloride dropwise and subsequently triethylamine
dropwise. To minimize exotherm and undesired side products,
careful control of the addition of reagents was achieved
through slow dropwise addition of these liquid reagents. Upon
complete consumption of starting materials and formation of amidooxime
39, the aqueous reaction mixture was then heated to
85 ?? to facilitate 1,2,4-oxadiazole formation, resulting in the tricyclic
ester 40 in excellent yield across the three steps. Finally,
saponification of ester 40 through the use of sodium hydroxide followed
by acidic quench gave ataluren (V) in 96% over the two-step
sequence.
Ataluren препаратная продукция и сырье
сырьё
препарат
Ataluren поставщик
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