MLN9708

그림문자(GHS)

• 그림문자(GHS)

  

• 신호 어

  Warning

• 유해·위험 문구

  H302：삼키면 유해함

  H315：피부에 자극을 일으킴

  H319：눈에 심한 자극을 일으킴

  H335：호흡 자극성을 일으킬 수 있음

• 예방조치문구

  P261：분진·흄·가스·미스트·증기·...·스프레이의 흡입을 피하시오.

  P305+P351+P338：눈에 묻으면 몇 분간 물로 조심해서 씻으시오. 가능하면 콘택트렌즈를 제거하시오. 계속 씻으시오.

MLN9708 화학적 특성, 용도, 생산

• 개요

  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.

• 용도

  MLN-9708 is a novel proteasome?inhibitor.

• Synthesis

  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 공급 업체

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