(E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-(naphthalen-1-yl)ethenesulfonamide | 403605-23-2

• 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-(naphthalen-1-yl)ethenesulfonamide
• 英文别名: (E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]-2-naphthalen-1-ylethenesulfonamide
• CAS: 403605-23-2
• 化学式: C₂₇H₂₀ClN₅O₄S
• 分子量: 546.006
• InChiKey: MJHQESBDMJZEHN-SAPNQHFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• 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：

  sodium methylate 、 (E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-(naphthalen-1-yl)ethenesulfonamide 以 甲醇 为溶剂， 以100%的产率得到(E)-2-Naphthalen-1-yl-ethenesulfonic acid [6-methoxy-5-(2-methoxy-phenoxy)-[2,2']bipyrimidinyl-4-yl]-amide
  参考文献：
  名称：

  Ethenesulfonamide and ethanesulfonamide derivatives, a novel class of orally active endothelin-A receptor antagonists

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(01)00187-0
• 作为产物：
  描述：

  4,6-二羟基-5-(2-甲氧基苯氧基)-2-(2-嘧啶基)嘧啶 在 2,4,6-三甲基嘧啶 、 sodium hydride 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.67h， 生成 (E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-(naphthalen-1-yl)ethenesulfonamide
  参考文献：
  名称：

  Ethenesulfonamide and ethanesulfonamide derivatives, a novel class of orally active endothelin-A receptor antagonists

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(01)00187-0

文献信息

• 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。
• US6083955A
  申请人：——

  公开号：US6083955A

  公开（公告）日：2000-07-04
• 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.