Ataluren (PTC124)

Bezeichnung:Ataluren (PTC124)

CAS-Nr775304-57-9

Englisch Name:Ataluren (PTC124)

CBNumberCB02128667

SummenformelC15H9FN2O3

Molgewicht284.24

MOL-Datei775304-57-9.mol

Ataluren (PTC124) physikalisch-chemischer Eigenschaften

Schmelzpunkt	241 - 242°C
Siedepunkt	503.7±60.0 °C(Predicted)
Dichte	1.379
storage temp.	Refrigerator
Löslichkeit	DMSO (Slightly)
Aggregatzustand	White to off-white solid.
pka	3.58±0.10(Predicted)
Farbe	White to Off-White
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)
InChIKey	OOUGLTULBSNHNF-UHFFFAOYSA-N
SMILES	C(O)(=O)C1=CC=CC(C2N=C(C3=CC=CC=C3F)ON=2)=C1
CAS Datenbank	775304-57-9

Sicherheit

HS Code

2933998090

Gefahreninformationscode (GHS)

Ataluren (PTC124) Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Beschreibung
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.
Verwenden
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]
Verwenden
PTC-124 is a nonaminoglycoside that has been reported to induce ribosomes to read through premature nonsense stop signals on mRNA, allowing the production of full-length functional proteins,
Definition
ChEBI: 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid is a ring assembly and an oxadiazole.
Synthese
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.
target
CFTR

Ataluren (PTC124) Upstream-Materialien And Downstream Produkte

Ataluren (PTC124) Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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