{4-[2-(4-Chloro-benzenesulfonylamino)-ethanesulfinyl]-2,6-difluoro-phenoxy}-acetic acid methyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: {4-[2-(4-Chloro-benzenesulfonylamino)-ethanesulfinyl]-2,6-difluoro-phenoxy}-acetic acid methyl ester
• 英文别名: Methyl 2-[4-[2-[(4-chlorophenyl)sulfonylamino]ethylsulfinyl]-2,6-difluorophenoxy]acetate
• 化学式: C₁₇H₁₆ClF₂NO₆S₂
• 分子量: 467.899
• InChiKey: AUMCAXAJHPHVPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  {4-[2-(4-Chloro-benzenesulfonylamino)-ethanesulfinyl]-2,6-difluoro-phenoxy}-acetic acid methyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 4-[2-(4-Chlorophenylsulfonylamino)ethylsulfinyl]-2,6-difluorophenoxylacetic acid
  参考文献：
  名称：

  Synthesis and evaluation of novel fluorinated sulotroban-related sulfonamide derivatives as thromboxane A2 receptor antagonists

  摘要：

  A series of sulotroban-related arylsulfonamide derivatives possessing a fluorinated phenoxyacetic acid moiety was synthesized and tested for TXA(2) antagonizing ability on U-46619-induced platelet aggregation of rabbit platelet-rich plasma. Introduction of one or more fluorine atoms to the phenoxyacetic acid moiety increased this activity. The most potent compound among these compounds was 10c, which was 40-fold more potent (IC50 3.4 x 10(-7) M) than sulotroban. 10c exhibited high activity (ID50, 0.14 mg/kg) against a U-46619-induced acute thrombocytopenia model in mice when orally administrated. These findings and those of radioligand binding assays with various ligands showed 10c to be a potent and selective systemic TXA, receptor antagonist.

  DOI：

  10.1016/0223-5234(96)88250-x
• 作为产物：
  描述：

  2,6-二氟苯酚 在 盐酸 、 氯磺酸 、 potassium carbonate 、 间氯过氧苯甲酸 、 tin(ll) chloride 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 141.5h， 生成 {4-[2-(4-Chloro-benzenesulfonylamino)-ethanesulfinyl]-2,6-difluoro-phenoxy}-acetic acid methyl ester
  参考文献：
  名称：

  Synthesis and evaluation of novel fluorinated sulotroban-related sulfonamide derivatives as thromboxane A2 receptor antagonists

  摘要：

  A series of sulotroban-related arylsulfonamide derivatives possessing a fluorinated phenoxyacetic acid moiety was synthesized and tested for TXA(2) antagonizing ability on U-46619-induced platelet aggregation of rabbit platelet-rich plasma. Introduction of one or more fluorine atoms to the phenoxyacetic acid moiety increased this activity. The most potent compound among these compounds was 10c, which was 40-fold more potent (IC50 3.4 x 10(-7) M) than sulotroban. 10c exhibited high activity (ID50, 0.14 mg/kg) against a U-46619-induced acute thrombocytopenia model in mice when orally administrated. These findings and those of radioligand binding assays with various ligands showed 10c to be a potent and selective systemic TXA, receptor antagonist.

  DOI：

  10.1016/0223-5234(96)88250-x

文献信息

• Asymmetric synthesis of the sulfoxide metabolite of ON-579 by the kagan protocol
  作者：Masakazu Sato、Akira Manaka、Yutaka Kawashima、Kazuyuki Tomisawa、Chuzo Iwata

  DOI：10.1016/s0960-894x(97)00456-3

  日期：1997.10

  A synthesis of both enantiomers of bio-active metabolite of ON-579; 4-[2-(4-chlorophenylsulfonylamino)-ethylsulfinyl]-2,6-difluorophnoxyacetic acid was accomplished by the asymmetric oxidation of ON-579 methyl eater followed by hydrolysis. Difference in TXA(2) receptor antagonizing activity was noted for the enantiomers in an U46619-induced rabbit platelet aggregation inhibitory activity. (C) 1997 Elsevier Science Ltd.
• Methyl Ester of the Bioactive Metabolite of Thromboxane A2 Receptor Antagonist ON-579
  作者：M. Sato、K. Matsumoto、Y. Kawashima、K. Tomisawa

  DOI：10.1107/s0108270198000158

  日期：1998.7.15

  The title compound, methyl (RS)-4-[2-(4-chlorophenyl-sulfonylamino) ethyisulfinyl]-2,6- difluorophenoxy}acetate, C17H16ClF2NO6S2, crystallizes in space group P2(1)/c. In the crystal, the enantiomeric molecules, related by a center of symmetry, form pairs joined by N-H ... O hydrogen bonds.
• Synthesis and evaluation of novel fluorinated sulotroban-related sulfonamide derivatives as thromboxane A2 receptor antagonists
  作者：M Sato、Y Kawashima、J Goto、Y Yamane、Y Chiba、S Jinno、M Satake、C Iwata

  DOI：10.1016/0223-5234(96)88250-x

  日期：1995.1

  A series of sulotroban-related arylsulfonamide derivatives possessing a fluorinated phenoxyacetic acid moiety was synthesized and tested for TXA(2) antagonizing ability on U-46619-induced platelet aggregation of rabbit platelet-rich plasma. Introduction of one or more fluorine atoms to the phenoxyacetic acid moiety increased this activity. The most potent compound among these compounds was 10c, which was 40-fold more potent (IC50 3.4 x 10(-7) M) than sulotroban. 10c exhibited high activity (ID50, 0.14 mg/kg) against a U-46619-induced acute thrombocytopenia model in mice when orally administrated. These findings and those of radioligand binding assays with various ligands showed 10c to be a potent and selective systemic TXA, receptor antagonist.