(E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide | 351019-39-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide
• 英文别名: (E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-3-phenylethenesulfonamide；N-[6-Chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]-2-phenylethenesulfonamide；(E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]-2-phenylethenesulfonamide
• CAS: 351019-39-1
• 化学式: C₂₃H₁₈ClN₅O₄S
• 分子量: 495.946
• InChiKey: CWVOUAFYMNAGJR-NTCAYCPXSA-N

物化性质

• 沸点：
  694.5±65.0 °C(Predicted)
• 密度：
  1.443±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide 在 盐酸 、 sodium 作用下， 以 2-丙炔-1-醇 为溶剂， 生成 N-[6-(2-propynyloxy)-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]-2-phenylethenesulfonamide
  参考文献：
  名称：

  Arylethenesulfonamide derivatives and drug composition containing the

  摘要：

  新型芳基乙烯磺酰胺衍生物具有高亲和力，特别是对药物和内源丝氨酸受体具有高亲和力，其通用式表示为（I）；其药学上可接受的盐；以及包含其作为活性成分的药物，特别是内源丝氨酸受体拮抗剂，其中 Ar：可选择取代的芳基或可选择取代的五元至六元杂芳基；X：氧原子、硫原子或由公式--NH--表示的基团；Y：氧原子或硫原子；R.sub.1：氢原子、可选择卤素取代的较低烷基基团、环烷基基团、可选择取代的芳基或可选择取代的五元至六元杂芳基；R.sub.2：较低烷基基团、较低烯基基团或较低炔基基团，其中每个基团可被选自氢氧基团、较低烷氧基团、环烷基基团、卤原子、羧基和较低烷氧羰基团的一到三个取代基取代；R.sub.3：苯基，可被选自可选择卤素取代的较低烷基基团、较低烷氧基团、卤原子、较低烷硫基团、较低烷基亚砜基团、较低烷烷基磺基团、羧基、较低烷氧羰基团和氨基基团的一到四个取代基取代；以及 R.sub.4 和 R.sub.5：它们可以相同也可以不同，每个都是氢原子或较低烷基。

  公开号：

  US06083955A1
• 作为产物：
  描述：

  (E)-(2-phenylethenyl)sulfonamide 、 波生坦中间体(I) 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以93%的产率得到(E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide
  参考文献：
  名称：

  Ethenesulfonamide Derivatives, a Novel Class of Orally Active Endothelin-A Receptor Antagonists

  摘要：

  在本文章中，我们希望报告通过改造ETA/ETB非选择性拮抗剂Ro47-0203（博生坦，1）发现一种新型ETA选择性内源性血管收缩素（ET）受体拮抗剂。将1的苯磺酰胺基团替换为2-苯基乙烯磺酰胺基团，得到化合物5a，并改善了ETA选择性。对连接在核心嘧啶环上的烷氧基侧链进行优化，得到2-氟乙氧基衍生物（5n），进一步提高了ETA选择性。[IC50 = 2.1 nM，ETB/ETA比率=1200]。口服给药后，化合物5n抑制了大剂量ET-1在麻醉大鼠中的压升反应，DR2值为2.6 mg/kg，并且在清醒的大鼠中表现出强效的拮抗活性。

  DOI：

  10.1248/cpb.49.606

文献信息

• NOVEL CRYSTAL OF ARYLETHENESULFONAMIDE DERIVATIVE AND PROCESS FOR PRODUCING THE SAME
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP1413578A1

  公开（公告）日：2004-04-28

  Novel crystals of a potassium salt of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide, a preparation process thereof, and novel solvates of (E)-N-[6-methoxy-5-(2-ethoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide.

  (E)-N-[6-甲氧基-5-(2-甲氧基苯氧基)-2-(嘧啶-2-基)嘧啶-4-基]-2-苯乙烯磺酰胺的钾盐新晶体、其制备方法，以及(E)-N-[6-甲氧基-5-(2-乙氧基苯氧基)-2-(嘧啶-2-基)嘧啶-4-基]-2-苯乙烯磺酰胺的新溶剂化合物。
• ARYLETHENESULFONAMIDE DERIVATIVES AND DRUG COMPOSITION CONTAINING THE SAME
  申请人：YAMANOUCHI PHARMACEUTICAL CO., LTD.

  公开号：EP0882719A1

  公开（公告）日：1998-12-09

  Novel arylethenesulfonamide derivatives having a high affinity for drugs, especially endoserine receptors, and represented by general formula (I); pharmacologically acceptable salts thereof; and drugs comprising the same as the active ingredient, especially endoserine receptor antagonists, wherein Ar represents optionally substituted aryl or optionally substituted five- or six-membered heteroaryl; X represents oxygen, sulfur, or the group represented by -NH-; Y represents oxygen or sulfur; R1 represents hydrogen, lower alkyl optionally substituted with halogeno, cycloalkyl, optionally substituted aryl, or optionally substituted five- or six-membered heteroaryl; R2 represents lower alkyl, lower alkenyl, or lower alkynyl each optionally substituted with one to three groups selected among hydroxy, lower alkoxys, cycloakyls, halogens, carboxy, and lower alkoxycarbonyls; R3 represents phenyl optionally substituted with one to four groups selected among optionally halogenated lower alkyls, lower alkoxys, halogens, lower alkylthios, lower alkylsulfinyls, lower alkanesulfonyls, carboxy, lower alkoxycarbonyls, and carbamoyl; and R4 and R5 are the same or different and each represents hydrogen or lower alkyl.

  通式(I)表示的对药物，特别是对内丝氨酸受体具有高亲和力的新型芳基乙烯磺酰胺衍生物；其药理学上可接受的盐；以及以其为活性成分的药物，特别是内丝氨酸受体拮抗剂，其中Ar代表任选取代的芳基或任选取代的五元或六元杂芳基；X 代表氧、硫或由 -NH- 代表的基团； Y 代表氧或硫； R1 代表氢、任选被卤素取代的低级烷基、环烷基、任选被取代的芳基或任选被取代的五元或六元杂芳基；R2 代表低级烷基、低级烯基或低级炔基，各自任选被一至三个选自羟基、低级烷氧基、环烷基、卤素、羧基和低级烷氧羰基的基团取代；R3 代表苯基，可任选被一至四个基团取代，这些基团选自任选卤化的低级烷基、低级烷氧基、卤素、低级烷硫基、低级烷基亚磺酰基、低级烷磺酰基、羧基、低级烷氧基羰基和氨基甲酰基；以及 R4 和 R5 相同或不同，各自代表氢或低级烷基。
• Novel crystal of arylethenesulfonamide derivative and preparation process thereof
  申请人：——

  公开号：US20040162302A1

  公开（公告）日：2004-08-19

  Novel crystals of a potassium salt of (E)-N-[6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide, a preparation process thereof, and novel solvates of (E)-N-[6-methoxy-5-(2-ethoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-phenylethenesulfonamide.

  (E)-N-[6-甲氧基-5-(2-甲氧基苯氧基)-2-(嘧啶-2-基)嘧啶-4-基&rsqb；-2-苯基乙烯磺酰胺、其制备方法以及(E)-N-[6-甲氧基-5-(2-乙氧基苯氧基)-2-(嘧啶-2-基)嘧啶-4-基]-2-苯基乙烯磺酰胺的新型溶胶。
• Ethenesulfonamide and ethanesulfonamide derivatives, a novel class of orally active endothelin-A receptor antagonists
  作者：Hironori Harada、Jun-ichi Kazami、Susumu Watanuki、Ryuji Tsuzuki、Katsumi Sudoh、Akira Fujimori、Masanao Sanagi、Masaya Orita、Hideaki Nakahara、Jun Shimaya、Shin-ichi Tsukamoto、Akihiro Tanaka、Isao Yanagisawa

  DOI：10.1016/s0968-0896(01)00187-0

  日期：2001.11

  In the previous paper, we described a series of 2-phenylethenesulfonamide derivatives, a novel class of ET(A)-selective endothelin (ET) receptor antagonists, including the 2-methoxyethoxy derivative 2a and the 2-fluoroethoxy derivative (2b). In this paper, we wish to report further details of structure-activity relationships (SARs) of the two regions of the molecule in compound 2b, which were the alkoxy region at the 6-position of the core pyrimidine ring and the 2-phenylethenesulfonamide region. In these modifications, replacement of the 2-fluoroethoxy group with a methoxy group (6e) and replacement of the 2-phenylethenesulfonamide group with a 2-(pyridin-3-yl)ethenesulfonamide group (61) or 2-phenylethanesulfonamide group (6q) were well tolerated both in the ET(A) binding affinity and ET(A) selectivity. Among them, compound 6e showed further improvement in oral activity compared to 2b. After oral administration, compound 6e inhibited the big ET-1 induced pressor response in conscious rats at 0.3 mg/kg with a duration of >6.5 h. Compound 6e also exhibited a potent antagonistic activity in the pithed rats. (C) 2001 Elsevier Science Ltd. All rights reserved.
• US6083955A
  申请人：——

  公开号：US6083955A

  公开（公告）日：2000-07-04