2-[4-(カルボキシメチル)-2-[(1S)-1-{2-[(2,5-ジクロロフェニル)ホルムアミド]アセトアミド}-3-メチルブチル]-5-オキソ-1,3,2-ジオキサボロラン-4-イル]酢酸

危険有害性情報のコード(GHS)

• 絵表示(GHS)

  

• 注意喚起語

  Warning

• 危険有害性情報

  H302：飲み込むと有害

  H315：皮膚刺激

  H319：強い眼刺激

  H335：呼吸器への刺激のおそれ

• 注意書き

  P261：粉じん/煙/ガス/ミスト/蒸気/スプレーの吸入を避ける こと。

  P305+P351+P338：眼に入った場合：水で数分間注意深く洗うこと。次にコ ンタクトレンズを着用していて容易に外せる場合は外す こと。その後も洗浄を続けること。

2-[4-(カルボキシメチル)-2-[(1S)-1-{2-[(2,5-ジクロロフェニル)ホルムアミド]アセトアミド}-3-メチルブチル]-5-オキソ-1,3,2-ジオキサボロラン-4-イル]酢酸 化学特性,用途語,生産方法

• 説明

  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.

• 使用

  MLN-9708 is a novel proteasome?inhibitor.

• 合成

  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.

  

2-[4-(カルボキシメチル)-2-[(1S)-1-{2-[(2,5-ジクロロフェニル)ホルムアミド]アセトアミド}-3-メチルブチル]-5-オキソ-1,3,2-ジオキサボロラン-4-イル]酢酸 生産企業

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2-[4-(カルボキシメチル)-2-[(1S)-1-{2-[(2,5-ジクロロフェニル)ホルムアミド]アセトアミド}-3-メチルブチル]-5-オキソ-1,3,2-ジオキサボロラン-4-イル]酢酸 スペクトルデータ(¹HNMR)

1201902-80-8, 2-[4-(カルボキシメチル)-2-[(1S)-1-{2-[(2,5-ジクロロフェニル)ホルムアミド]アセトアミド}-3-メチルブチル]-5-オキソ-1,3,2-ジオキサボロラン-4-イル]酢酸 キーワード