4-<2-(4-chlorophenylsulfonylamino)ethylthio>-2,6-difluorophenoxyacetamide

• 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)ethylthio>-2,6-difluorophenoxyacetamide
• 英文别名: 4-[2-(4-chlorophenylsulfonylamino)ethylthio]-2,6-difluorophenoxyacetamide；2-[4-[2-[(4-chlorophenyl)sulfonylamino]ethylsulfanyl]-2,6-difluorophenoxy]acetamide
• 化学式: C₁₆H₁₅ClF₂N₂O₄S₂
• 分子量: 436.888
• InChiKey: PXYKSSWHABENJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 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：
  132
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,6-二氟苯酚 在 盐酸 、 氯磺酸 、 ammonium hydroxide 、 potassium carbonate 、 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-chlorophenylsulfonylamino)ethylthio>-2,6-difluorophenoxyacetamide
  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：US05189211A1

  公开（公告）日：1993-02-23

  A sulfonamide derivative represented by the Formula: ##STR1## wherein A, B, X, Y, R, m and n are as defined in the specification, and a salt thereof have thromboxane A.sub.2 antagonism, therefore they are useful, for example, as blood platelet aggregation inhibiting agents.

  一种由以下式表示的磺胺衍生物：##STR1## 其中A、B、X、Y、R、m和n如规范中所定义，并且其盐具有血栓素A.sub.2拮抗作用，因此它们可用作例如血小板聚集抑制剂。
• Glutamic acid receptor agonist
  申请人：Nippon Suisan Kaisha, Ltd.

  公开号：US05955505A1

  公开（公告）日：1999-09-21

  A method comprising administering a sulfonamide derivative to a patient requiring activation of glutamate receptors, the sulfonamide derivative represented by the formula ##STR1## wherein A is a napthyl group, a pyridyl group, a phenyl group, a phenyl group substituted by 1 to 5 members selected from the group consisting of a halogen atom, an alkyl group having 1 to 40 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, and an acetamido group, or an alkyl group having 1 to 20 carbon atoms; B is an alkylene group having 1 to 3 carbon atoms, a group of --OCH.sub.2 -- or a group of --CH.dbd.CH--; X and Y are the same or different, and are each a hydrogen atom or a fluorine atom; R is a carboxy group, an alkoxycarbonyl group having 2 to 5 carbon atoms, a hydroxymethyl group or a group of ##STR2## wherein R.sub.1 is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms; and R.sub.2 is a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms, a carboxymethyl group or an alkoxycarbonylmethyl group having 3 to 6 carbon atoms; m is an integer from 0 to 2; and n is an integer from 0 to 3, or an pharmaceutically acceptable salt thereof, as an effective ingredient. The agonist is efficacious in the medical treatment of nerve degenerative disorders.

  一种方法包括向需要激活谷氨酸受体的患者施用磺胺衍生物，所述磺胺衍生物由以下式表示：其中A为萘基、吡啶基、苯基、被1至5个成员选自卤原子、具有1至40个碳原子的烷基、具有1至4个碳原子的烷氧基、硝基和乙酰氨基的苯基取代的苯基，或者具有1至20个碳原子的烷基；B为具有1至3个碳原子的烷基、--OCH.sub.2--基团或--CH.dbd.CH--基团；X和Y相同或不同，分别为氢原子或氟原子；R为羧基、具有2至5个碳原子的烷氧羰基、羟甲基基团或##STR2##基团，其中R.sub.1为氢原子或具有1至3个碳原子的烷基；R.sub.2为氢原子、羟基、具有1至3个碳原子的烷基、羧甲基基团或具有3至6个碳原子的烷氧羰基甲基基团；m为0至2的整数；n为0至3的整数，或其药学上可接受的盐，作为有效成分。该激动剂在神经退行性疾病的医疗治疗中具有疗效。
• 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。
• NOVEL COMPOUND THAT SPECIFICALLY BINDS TO AMPA RECEPTOR
  申请人：Public University Corporation Yokohama City University

  公开号：EP3321252A1

  公开（公告）日：2018-05-16

  The present invention provides a compound represented by formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof. (In the formula, each of A and Z independently represents CO, SO or SO2; each of X and Y independently represents S or O; each of R1-R4 independently represents hydrogen, alkyl, alkenyl, alkynyl or halo; each R5 independently represents alkyl, alkenyl, alkynyl or halo; and n represents an integer of 0-4.) This compound is capable of specifically binding to an AMPA receptor, and shows extremely high brain uptake.

  本发明提供了一种由式 (I) 代表的化合物、其药学上可接受的盐或其溶液。 (式中，A和Z各自独立地代表CO、SO或SO2；X和Y各自独立地代表S或O；R1-R4各自独立地代表氢、烷基、烯基、炔基或卤代物；R5各自独立地代表烷基、烯基、炔基或卤代物；n代表0-4的整数)。这种化合物能够特异性地与 AMPA 受体结合，并显示出极高的脑吸收率。
• PROPHYLACTIC AND/OR THERAPEUTIC AGENT FOR DISEASES ASSOCIATED WITH AMPA RECEPTORS
  申请人：Public University Corporation Yokohama City University

  公开号：EP3569229A1

  公开（公告）日：2019-11-20

  This prophylactic and/or therapeutic agent for diseases associated with AMPA receptors contains a compound represented by formula (I), or a pharmaceutically acceptable salt or solvate thereof. (In the formula, A and Z independently represent CO, SO or SO2; X and Y are independently S or O; R1-R4 are independently hydrogen, an alkyl group, an alkenyl group, an alkynyl group or a halo group; R5 is, independently for each occurrence, an alkyl group, an alkenyl group, an alkynyl group or a halo group; and n is an integer of 0-4).

  这种与 AMPA 受体相关疾病的预防和/或治疗剂含有由式 (I) 代表的化合物或其药学上可接受的盐或溶液。(式中，A 和 Z 独立地代表 CO、SO 或 SO2；X 和 Y 独立地为 S 或 O；R1-R4 独立地为氢、烷基、烯基、炔基或卤代基团；R5 在每次出现时独立地为烷基、烯基、炔基或卤代基团；n 为 0-4 的整数）。