福司曲星 | 87810-56-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 中文名称: 福司曲星
• 中文别名: 佛司曲辛
• 英文名称: fostriecin
• 英文别名: CI-920；[(1E,3R,4R,6R,7Z,9Z,11E)-3,6,13-trihydroxy-3-methyl-1-[(2R)-6-oxo-2,3-dihydropyran-2-yl]trideca-1,7,9,11-tetraen-4-yl] dihydrogen phosphate
• CAS: 87810-56-8
• 化学式: C₁₉H₂₇O₉P
• 分子量: 430.392
• InChiKey: ZMQRJWIYMXZORG-DSWNLJKISA-N

物化性质

• 沸点：
  737.9±70.0 °C(Predicted)
• 密度：
  1.413±0.06 g/cm3(Predicted)
• 溶解度：
  Water > 300 (mg/mL)
• 稳定性/保质期：
  Bulk: Decomposition was not observed when the bulk drug was frozen1 and stored for 23 months in the presence of one molar equivalent of sodium ascorbate. Solution: At low concentrations (1.0 mg/mL or less) in the presence of sodium ascorbate, potency is retained upon storage at 5 °C for up to three weeks. The compound is most stable in the pH range 4-8, with rapid decomposition occurring in both strongly acidic and strongly basic solutions.

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  154
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  福司曲星 在 Stryker's reagent 、 水 作用下， 以 乙醇 为溶剂， 反应 4.5h， 以86%的产率得到(5R,6E,8R,9R,11R,12Z,14Z,16E)-5,8,11,18-tetrahydroxy-8-methyl-9-phosphonooxyoctadeca-6,12,14,16-tetraenoic acid
  参考文献：
  名称：

  Fundamental Role of the Fostriecin Unsaturated Lactone and Implications for Selective Protein Phosphatase Inhibition

  摘要：

  Key derivatives and analogues of fostriecin were prepared and examined that revealed a fundamental role for the unsaturated lactone and confirmed the essential nature of the phosphate monoester. Thus, an identical 200-fold reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the saturated lactone (7) or with an analogue that lacks the entire lactone (15). This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone potentially may be due to reversible C269 alkylation within the PP beta12-beta13 active site loop accounting for PP2A/4 potency and selectivity.

  DOI：

  10.1021/ja038672n
• 作为产物：
  描述：

  Phosphoric acid mono-{(4Z,6Z,8E)-(1R,3R)-3-(tert-butyl-dimethyl-silanyloxy)-10-(tert-butyl-diphenyl-silanyloxy)-1-[(E)-(R)-1-methyl-3-((R)-6-oxo-3,6-dihydro-2H-pyran-2-yl)-1-triethylsilanyloxy-allyl]-deca-4,6,8-trienyl} ester 在 吡啶 、 氢氟酸 作用下， 以 乙腈 为溶剂， 以79%的产率得到福司曲星
  参考文献：
  名称：

  Versatile enantiocontrolled synthesis of (+)-fostriecinElectronic supplementary information (ESI) available: experimental section. See http://www.rsc.org/suppdata/cc/b2/b209742g/

  摘要：

  富司曲辛，一种强效蛋白磷酸酶抑制剂和抗肿瘤药物，已通过一种多功能途径被选择性地合成为其天然存在形式，该途径还使得人们能够获得C1-C13片段中包括C11立体中心和Δ12双键几何结构在内的所有可能的立体异构体。

  DOI：

  10.1039/b209742g

文献信息

• Total Synthesis of (+)-Fostriecin and (+)-Phoslactomycin B
  作者：Susumi Hatakeyama、Setsuya Shibahara、Masataka Fujino、Yasumasa Tashiro、Nanako Okamoto、Tomoyuki Esumi、Keisuske Takahashi、Jun Ishihara

  DOI：10.1055/s-0029-1216930

  日期：2009.9

  (+)-Fostriecin and (+)-phoslactomycin B, which are potent and selective inhibitors of protein phosphatase, were synthesized by a highly enantio- and stereoselective approach that enabled us to prepare all possible isomers at both the C11 secondary alcohol position and the Δ¹²-double bond.

  (+)-Fostriecin 和 (+)-phoslactomycin B，作为蛋白磷酸酶的有效且选择性抑制剂，是通过高度对映选择性和立体选择性的方法合成的，这种方法使我们能够制备在 C11 次级醇位置和 Δ¹² 双键处的所有可能异构体。
• Total synthesis of fostriecin (CI-920) via a convergent route
  作者：Kazuyuki Miyashita、Masahiro Ikejiri、Hitomi Kawasaki、Satoko Maemura、Takeshi Imanishi

  DOI：10.1039/b201302a

  日期：2002.3.21

  Fostriecin, a potent and promising antitumor antibiotic, was stereoselectively synthesized via a convergent route involving a three-segement coupling procedure.

  福斯替辛是一种有效且前景广阔的抗肿瘤抗生素，其立体选择性合成是通过三段偶联程序的聚合路线实现的。
• Total Synthesis of Fostriecin (CI-920)
  作者：Dale L. Boger、Satoshi Ichikawa、Wenge Zhong

  DOI：10.1021/ja010195q

  日期：2001.5.1

  The first total synthesis of the potent antitumor agent fostriecin (CI-920) is described, confirming the relative and absolute stereochemistry assignments. Fostriecin is a unique phosphate monoester which exhibits weak topoisomerase II inhibition (IC50 = 40 μM) and more potent and selective protein phosphatase 2A and 4 (PP2A and PP4) inhibition (IC50 = 40−3 nM and 1.5 nM), resulting in mitotic entry

  描述了强效抗肿瘤剂 fostriecin (CI-920) 的首次全合成，确认了相对和绝对立体化学分配。Fostriecin 是一种独特的磷酸单酯，表现出弱拓扑异构酶 II 抑制 (IC50 = 40 μM) 和更有效和选择性的蛋白磷酸酶 2A 和 4（PP2A 和 PP4）抑制（IC50 = 40-3 nM 和 1.5 nM），导致有丝分裂进入检查点抑制。由于在天然衍生材料的储存过程中观察到药物稳定性问题，甚至在达到治疗浓度或确定剂量限制毒性之前，使用 Festriecin 的 I 期临床试验是第一个探索这种新作用机制的潜力的试验。
• FOSTRIECIN DERIVATIVES AND THE PHARMACEUTICAL USES THEREOF
  申请人：Tang Li

  公开号：US20120065171A1

  公开（公告）日：2012-03-15

  Novel Fostriecin (or FST) derivatives represented by formula (I), the pharmaceutical compositions and preparation methods thereof. The pharmaceutical uses of these compounds, especially the use for the preparation of pharmaceutical compositions for treating tumor, inhibiting cell over growth, or lowering myocardial infarction and the injury to cells.

  Novel Fostriecin（或FST）衍生物由公式（I）表示，其药物组成物和制备方法。这些化合物的药物用途，特别是用于制备治疗肿瘤，抑制细胞过度生长或降低心肌梗死和细胞损伤的药物组合物。
• COMPOSITIONS, METHODS AND SYSTEMS FOR THE TREATMENT OF CUTANEOUS DISORDERS
  申请人：VERRICA PHARMACEUTICALS, INC.

  公开号：US20160193177A1

  公开（公告）日：2016-07-07

  Provided herein are devices, systems, kits and methods for treating skin conditions, ailments or diseases, such as skin warts. In some examples, a device for treating warts comprises a reservoir that includes a cantharidin formulation, and an applicator device in fluid communication with the reservoir that delivers the cantharidin formulation to a subject.