Vonoprazan fumarate

化学名:Vonoprazan fumarate

CAS番号.1260141-27-2

英語名:Vonoprazan fumarate

CBNumberCB32628441

MFC21H20FN3O6S

MW461.4634032

MOL File1260141-27-2.mol

Vonoprazan fumarate物理性質

貯蔵温度	Store at -20°C
溶解性	insoluble in H2O; insoluble in EtOH; ≥18.9 mg/mL in DMSO
外見	solid
InChIKey	ROGSHYHKHPCCJW-WLHGVMLRSA-N
SMILES	N1(S(C2=CC=CN=C2)(=O)=O)C(C2=CC=CC=C2F)=CC(CNC)=C1.C(O)(=O)/C=C/C(O)=O

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

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。

P264：取扱い後は皮膚をよく洗うこと。

P264：取扱い後は手や顔をよく洗うこと。

P271：屋外または換気の良い場所でのみ使用すること。

P280：保護手袋/保護衣/保護眼鏡/保護面を着用すること。

P302+P352：皮膚に付着した場合：多量の水と石鹸で洗うこと。

P304+P340：吸入した場合：空気の新鮮な場所に移し、呼吸しやすい姿勢で休息させること。

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。

P312：気分が悪い時は医師に連絡すること。

P321：特別な処置が必要である（このラベルの．．．を見よ）。

P332+P313：皮膚刺激が生じた場合：医師の診断/手当てを受けること。

P337+P313：眼の刺激が続く場合：医師の診断/手当てを受けること。

P403+P233：換気の良い場所で保管すること。容器を密閉しておくこと。

P405：施錠して保管すること。

P501：内容物/容器を．．．に廃棄すること。

Vonoprazan fumarate 化学特性,用途語,生産方法

説明
Vonoprazan fumarate (Takecab®), discovered and developed by Takeda and Otsuka, was approved by the PMDA of Japan in December 2014, and is indicated for the treatment of gastric ulcer, duodenal ulcer and reflux esophagitis. Vonoprazan fumarate has a novel mechanism of action called potassium-competitive acid blockers, which competitively inhibit the binding of potassium ions to H+, K+-ATPase (also known as the proton pump) in the final step of gastric acid secretion in gastric parietal cells. Vonoprazan does not inhibit Na+, K+-ATPase activity even at concentrations 500 times higher than that of their IC50 values against gastric H+, K+-ATPase activity. Furthermore, the drug is unaffected by the gastric secretory state, unlike PPIs.
使用
Vonoprazan Fumarate is a novel potassium-?competitive acid blocker for the treatment of acid-?related diseases.
主な応用
Vonoprazan fumarate is an oral, newly synthesised potassium-competitive acid blocker (P-CAB) with antisecretory activity. It is also a proton pump inhibitor (PPI) reversibly inhibiting H+/K+, ATPase. It is mainly used in the treatment of acid-related diseases such as GERD and peptic ulcer disease.
合成
Commercially available 2-fluoroacetophenone (283) was brominated to yield a-bromo-acetophenone derivative 284. This compound was treated with ethyl 2-cyanoacetate (285) under basic conditions to provide ketoester 286 in essentially quantitative yield. Next, intramolecular condensation of 286 upon treatment of 4 M HCl furnished the tri-substituted pyrrole 287 in 53% yield. Reduction of the chloride under hydrogenolytic conditions facilitated arrival at pyrrole 288, albeit in just 18% yield. Subsequent diisobutylaluminium hydride (DIBAL) reduction, followed by the oxidation with tetrapropylammonium perruthenate (TPAP) and 4-methylmorpholine N-oxide (NMMO) afforded the corresponding aldehyde 290 in 60% yield across the 2 steps. Next, N-pyrrole substitution with pyridine- 3-sulfonyl chloride 291 gave rise to N-sulfonylpyrrole 292 in 82% yield. Reductive amination of 292 afforded amine 293, which was treated with fumaric acid (294) via co-crystallization to provide vonoprazan fumarate (XXXVI) in 74% for the two steps.

Vonoprazan fumarate 生産企業

1260141-27-2, Vonoprazan fumarate キーワード

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