4-tert-Butyl-N-[6-chloro-5-(3-methoxy-phenoxy)-2-methyl-pyrimidin-4-yl]-benzenesulfonamide | 189574-47-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-tert-Butyl-N-[6-chloro-5-(3-methoxy-phenoxy)-2-methyl-pyrimidin-4-yl]-benzenesulfonamide
• 英文别名: 4-tert-butyl-N-[6-chloro-5-(3-methoxyphenoxy)-2-methylpyrimidin-4-yl]benzenesulfonamide
• CAS: 189574-47-8
• 化学式: C₂₂H₂₄ClN₃O₄S
• 分子量: 461.969
• InChiKey: VOGWDGTWVKQZDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  98.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-tert-Butyl-N-[6-chloro-5-(3-methoxy-phenoxy)-2-methyl-pyrimidin-4-yl]-benzenesulfonamide 在 sodium hydride 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 8.5h， 生成 4-tert-Butyl-N-[5-(3-methoxy-phenoxy)-2-methyl-6-(4-oxo-butoxy)-pyrimidin-4-yl]-benzenesulfonamide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of potent and orally active sulfonamide ETB selective antagonists

  摘要：

  The synthesis and structure-activity relationships of a series of N-pyrimidinyl benzenesulfonamides as ETB selective antagonists are described. N-Isoxazolyl benzenesulfonamide 1a. previously reported,(1) was selected as a lead compound, and isosteric replacement of the isoxazole ring of la with a pyrimidine ring led to the discovery of the highly potent ETB selective antagonist 6e with oral bioavailability. Modification of the terminal aldehyde group at the 6-position of the pyrimidine ring was investigated, and malonate 15b and acylhydrazone 16f were found to be equipotent to aldehyde 6e. Compound 6e showed ETB antagonistic activity on in vivo evaluation. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00305-9
• 作为产物：
  描述：

  m-methoxyphenoldimethyl 3-methoxyphenoxymalonate 在 2,3,5-三甲基吡啶 、 sodium methylate 、 三氯氧磷 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 7.0h， 生成 4-tert-Butyl-N-[6-chloro-5-(3-methoxy-phenoxy)-2-methyl-pyrimidin-4-yl]-benzenesulfonamide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of potent and orally active sulfonamide ETB selective antagonists

  摘要：

  The synthesis and structure-activity relationships of a series of N-pyrimidinyl benzenesulfonamides as ETB selective antagonists are described. N-Isoxazolyl benzenesulfonamide 1a. previously reported,(1) was selected as a lead compound, and isosteric replacement of the isoxazole ring of la with a pyrimidine ring led to the discovery of the highly potent ETB selective antagonist 6e with oral bioavailability. Modification of the terminal aldehyde group at the 6-position of the pyrimidine ring was investigated, and malonate 15b and acylhydrazone 16f were found to be equipotent to aldehyde 6e. Compound 6e showed ETB antagonistic activity on in vivo evaluation. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00305-9

文献信息

• N-(Pyrimidinyl)-benzolsulfonamide als Arzneimittel
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0768304A1

  公开（公告）日：1997-04-16

  Verbindungen der allgemeinen Formel    worin R1-R6, Ra, Rb, X, Y, Z, m und n die in der Beschreibung gegebene Bedeutung haben, können als Heilmittel, insbesondere zur Behandlung von mit Endothelinaktivitäten assozierten Aktivitätenzuständen, Verwendung finden.

  通式如下的化合物 其中 R1-R6、Ra、Rb、X、Y、Z、m 和 n 具有说明中给出的含义、 可用作治疗剂，特别是用于治疗与内皮素活性相关的活动状态。
• Synthesis and structure–activity relationships of potent and orally active sulfonamide ETB selective antagonists
  作者：Yasuhiko Kanda、Yasuyuki Kawanishi、Katsuo Oda、Teruo Sakata、Shin-ichi Mihara、Kenji Asakura、Toshiyuki Kanemasa、Mitsuyoshi Ninomiya、Masafumi Fujimoto、Toshiro Konoike

  DOI：10.1016/s0968-0896(00)00305-9

  日期：2001.4

  The synthesis and structure-activity relationships of a series of N-pyrimidinyl benzenesulfonamides as ETB selective antagonists are described. N-Isoxazolyl benzenesulfonamide 1a. previously reported,(1) was selected as a lead compound, and isosteric replacement of the isoxazole ring of la with a pyrimidine ring led to the discovery of the highly potent ETB selective antagonist 6e with oral bioavailability. Modification of the terminal aldehyde group at the 6-position of the pyrimidine ring was investigated, and malonate 15b and acylhydrazone 16f were found to be equipotent to aldehyde 6e. Compound 6e showed ETB antagonistic activity on in vivo evaluation. (C) 2001 Elsevier Science Ltd. All rights reserved.