ブレポシチニブ 化学特性,用途語,生産方法
効能
抗炎症薬, チロシンキナーゼ阻害薬
特性
Class: non-receptor tyrosine kinase
Treatment: immunological disorders
Other name: PF-06700841; Brepocitinib
Elimination half-life = 3.8–7.5 h
Protein binding = 39%
使用
PF-06700841 tosylate salt has been used as an inhibitor of Janus kinase1 (JAK1) to study its therapeutic effect on the adjuvant induced arthritis (AIA) rat model. It has also been used as an inhibitor of interferon-α/β receptor alpha chain (IFNAR1) signaling adaptor tyrosine kinase (2TYK2) in mice.
Biochem/physiol Actions
PF-06700841 prevents IL-23 (interleukin 23) signaling through TYK2 (Tyrosine-protein kinase 2)/JAK1 (Janus kinase 1) inhibition.
安全性
Brepocitinib(PF-06700841) was generally effective and well tolerated in patients with moderate-to-severe plaque psoriasis.
合成
Brepocitinib(PF06700841) can be synthesized as follows :
Add 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-N-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-amine hydrochloride (700 mg), HATU (1.02 g, 2.61 mmol) and DIPEA (0.76 mL, 4.34 mmol) to a solution of (S)-2,2-difluorocyclopropane-1-carboxylic acid (318 mg) in DCM (20 mL);
Stir the reaction at room temperature for 18 hours;
Dilute the reaction with DCM and saturated aqueous ammonium chloride solution;
Separate the organic layer;
Wash the organic layer with ammonium chloride solution;
Concentrate the organic layer in vacuo;
Purify the residue using silica gel column chromatography eluting with 0-12% MeOH and 1% NH4OH in DCM;
Dissolve the residue in DCM;
Wash the residue with saturated aqueous ammonium chloride solution three times;
Collect the organic layer;
Concentrate the organic layer in vacuo;
Dry the organic layer.
ブレポシチニブ 上流と下流の製品情報
原材料
準備製品