MLN9708

Bezeichnung:MLN9708

CAS-Nr1201902-80-8

Englisch Name:MLN9708

CBNumberCB82521079

SummenformelC20H23BCl2N2O9

Molgewicht517.12

MOL-Datei1201902-80-8.mol

MLN9708 physikalisch-chemischer Eigenschaften

Schmelzpunkt	>227°C (dec.)
Dichte	1.47
storage temp.	Hygroscopic, -20°C Freezer, Under inert atmosphere
Löslichkeit	DMSO (Slightly), Methanol (Slightly, Heated, Sonicated)
pka	1.92±0.20(Predicted)
Aggregatzustand	Solid
Farbe	White to Off-White

Sicherheit

S-Sätze:	24/25
HS Code	29329990

Gefahreninformationscode (GHS)

MLN9708 Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Ixazomib citrate is a proteasome inhibitor prodrug for the treatment of multiple myeloma in patients who have received at least one prior therapy in combination with lenalidomide and dexamethasone. The drug was developed by Takeda and reversibly inhibits the protein proteasome subunit β type-5, which is part of the 20S proteasome complex. Ixazomib citrate (XXIV) is hydrolyzed quickly in vivo to give the biologically active compound ixazomib, which presumably is the corresponding boronic acid variant of XXIV.
Verwenden
MLN-9708 is a novel proteasome?inhibitor.
Clinical Use
Highly selective and reversible proteasome inhibitor:
Treatment of multiple myeloma in combination with lenalidomide and dexamethasone
Synthese
The structure of ixazomib citrate is particularly interesting in that it is one of the relatively few marketed drugs which feature a boron atom within its structure (others of note being the oncology medication bortezomib and the antifungal drug tavaborole13). The ostensible scale synthetic approach began with reaction of commercial 2,5-dichlorobenzoyl chloride (188) with glycine in aqueous NaOH to furnish amide 189 in 97% yield as a white crystalline solid. Acid 189 was then coupled with commercially available 1,3,2-benzodioxaborolane 190 in the presence of TBTU and DIPEA in DMF at low temperature to give diamide 191, which was used without purification for the next step. Borane 191 was then deprotected with (2-methylpropyl)boronic acid in methanolic HCl to provide trimer 192 in 74% as a white solid. Finally, boroxin 192 was reacted with citric acid in EtOAc to dissociate the trimer, resulting in ixazomib citrate (XXIV) in 88% yield as a crystalline solid.

MLN9708 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

1201902-80-8, MLN9708 Verwandte Suche:

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