トホグリフロジン水和物

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。

トホグリフロジン水和物 化学特性,用途語,生産方法

• 効能

  糖尿病治療薬, SGLT-2阻害薬

• 商品名

  アプルウェイ (サノフィ); デベルザ (興和)

• 説明

  Tofogliflozin hydrate, which is a sodium-glucose co-transporter 2 inhibitor, was approved in Japan for the treatment of type 2 diabetes at the same time as luseogliflozin hydrate (XIX). The drug was discovered by Chugai Pharmaceutical and jointly developed with Sanofi-Aventis and Kowa. Tofogliflozin hydrate reduces glucose levels by inhibiting the reuptake of glucose by selectively inhibiting SGLT2, and plays a key role in the reuptake of glucose in the proximal tubule of the kidneys.

• 合成

  Reduction of commercially available 2-bromoterephtalic acid (268) through the use of trimethoxyborane and borane- THF proceeded in 89% yield to afford diol 269. Subjection of this compound to 2-methoxypropene (270) under acidic conditions generated bis-acetonide 271. This bromide then underwent lithium¨Chalogen exchange followed by exposure to magnesium bromide and treatment with lactone 272 (which was prepared by persilylation of commercially available (3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2Hpyran- 2-one (277). This mixture was worked up with aqueous ammonium chloride and upon treatment with p-TsOH in methanol resulted in spiroacetal 273. Next, global protection of all alcohol functionalities within 273 was affected by reaction with methylchloroformate and DMAP in acetonitrile. The benzyl carbonate within 274 was selectively exchanged via Suzuki coupling with 4-ethylphenylboronic acid (275) to afford methylene dibenzyl system 276. Subsequent treatment with aqueous sodium hydroxide in methanol followed by crystallization from 1:6 acetone and water furnished the desired product tofogliflozin hydrate (XXXIV) in 75% yield.

  

トホグリフロジン水和物 生産企業

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トホグリフロジン水和物 スペクトルデータ(¹HNMR)

1201913-82-7, トホグリフロジン水和物 キーワード