4-[2-(4-Chlorophenylsulfonylamino)ethylsulfinyl]-2,6-difluorophenoxylacetic acid

• 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-Chlorophenylsulfonylamino)ethylsulfinyl]-2,6-difluorophenoxylacetic acid
• 英文别名: 4-[2-(4-Chlorophenylsulfonylamino)ethylsulfinyl]-2,6-difluorophenoxyacetic acid；2-[4-[2-[(4-Chlorophenyl)sulfonylamino]ethylsulfinyl]-2,6-difluorophenoxy]acetic acid
• 化学式: C₁₆H₁₄ClF₂NO₆S₂
• 分子量: 453.872
• InChiKey: MISKQWYLWKXYRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,6-二氟苯酚 在 盐酸 、 氯磺酸 、 sodium hydroxide 、 potassium carbonate 、 间氯过氧苯甲酸 、 tin(ll) chloride 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 142.5h， 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

文献信息

• Sulfonamide derivatives
  申请人：TAISHO PHARMACEUTICAL CO. LTD

  公开号：EP0469901A1

  公开（公告）日：1992-02-05

  Sulfonamide derivative, useful as blood platelet aggregation inhibitors, have the formula: in which A is a naphthyl group, a pyridyl group, a phenyl group, a phenyl group substituted by 1 to 5 substituents selected from halogen atoms, alkyl groups having 1 to 4 carbon atoms, alkoxy groups having 1 to 4 carbon atoms, nitro groups and acetamido groups, or an alkyl group having 1 to 20 carbon atoms; B is an alkylene group having 1 to 3 carbon atoms, a group -OCH₂- or a group -CH=CH-; X and Y are the same or different, and each is a hydrogen or fluorine atom; R is a carboxy group, an alkyoxycarbonyl group having 2 to 5 carbon atoms, a hydroxymethyl group or a group of the formula (in which R¹ is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms; R² is a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms, a carboxymethyl group or an alkoycarbonylmethyl group having 3 to 6 carbon atoms); m is 0, 1 or 2; n is 0,1,2 or 3; or salts thereof. This invention also provided intermediates for the preparation of the sulfonamide, which intermediates are thiophenols of the formula: (in which R, X and Y are as defined above).

  磺酰胺衍生物可用作血小板聚集抑制剂，其化学式为 其中 A 是萘基、吡啶基、苯基、被 1 至 5 个取代基取代的苯基，取代基可选 自卤素原子、1 至 4 个碳原子的烷基、1 至 4 个碳原子的烷氧基、硝基和乙酰氨基， 或 1 至 20 个碳原子的烷基；B 是具有 1 至 3 个碳原子的亚烷基、基团-OCH₂- 或基团-CH=CH-； X 和 Y 相同或不同，各自是氢原子或氟原子； R 是羧基、具有 2 至 5 个碳原子的烷氧羰基、羟甲基或式如下的基团 (其中，R¹是氢原子或具有 1 至 3 个碳原子的烷基；R²是氢原子、羟基、具有 1 至 3 个碳原子的烷基、羧甲基或具有 3 至 6 个碳原子的烷酰基甲基）；m 是 0、1 或 2；n 是 0、1、2 或 3；或其盐。 本发明还提供了制备磺酰胺的中间体，这些中间体是式中的噻吩酚： (其中 R、X 和 Y 如上定义）。
• GLUTAMIC ACID RECEPTOR AGONIST
  申请人：NIPPON SUISAN KAISHA, LTD.

  公开号：EP0811375A1

  公开（公告）日：1997-12-10

  A glutamic acid receptor agonist which comprises as the active ingredient sulfonamide derivatives represented by general formula (I) or pharmaceutically acceptable salts thereof wherein A represents naphthyl, pyridyl, phenyl optionally having 1 to 5 substituents selected from the group consisting of halogeno, C1-4 alkyl, C1-4 alkoxy, nitro and acetamido, or C¿1-20 alkyl; B represents C¿1-3 alkylene, -OCH2- or -CH=CH-; X and Y are the same or different and each represents hydrogen or fluoro; R represents carboxy, C2-5 alkoxycarbonyl, hydroxymethyl or (a) (wherein R1 represents hydrogen or C1-3 alkyl; and R2¿ represents hydrogen, hydroxy, C1-3 alkyl, carboxymethyl or C¿3-6 alkoxycarbonyl); m represents an integer of 0 to 2 and n represents an integer of 0 to 3. The agonist is efficatious in the prevention and treatment of nerve degeneration in morbid conditions.

  一种谷氨酸受体激动剂，其活性成分包括通式(I)所代表的磺酰胺衍生物或其药学上可接受的盐 其中A代表萘基、吡啶基、苯基，可任选具有1至5个取代基，这些取代基选自由卤素、C1-4烷基、C1-4烷氧基、硝基和乙酰氨基或C¿1-20烷基组成的组；B代表C¿1-3亚烷基、-OCH2-或-CH＝CH-；X和Y相同或不同，各自代表氢或氟；R代表羧基、C2-5烷氧基羰基、羟甲基或(a)（其中R1代表氢或C1-3烷基；R2¿代表氢、羟基、C1-3烷基、羧甲基或C¿3-6烷氧基羰基）；m代表0至2的整数，n代表0至3的整数。该激动剂对预防和治疗病态情况下的神经变性具有疗效。
• 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.
• US5189211A
  申请人：——

  公开号：US5189211A

  公开（公告）日：1993-02-23
• 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.