4-叔丁基-N-{6-氯-5-(3-甲氧基苯氧基)嘧啶-4-基}苯磺酰胺 | 150727-29-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-叔丁基-N-{6-氯-5-(3-甲氧基苯氧基)嘧啶-4-基}苯磺酰胺
• 英文名称: 4-tert-butyl-N-{6-chloro-5-(3-methoxyphenoxy)pyrimidin-4-yl}benzenesulfonamide
• 英文别名: 4-tert-butyl-N-(6-chloro-5-(3-methoxyphenoxy)-4-pyrimidinyl)benzenesulfonamide；4-tert-butyl-N-[6-chloro-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide；p-t-butyl-N-[6-chloro-5-(m-methoxyphenoxy)-4-pyrimidinyl]benzenesulfonamide
• CAS: 150727-29-0
• 化学式: C₂₁H₂₂ClN₃O₄S
• 分子量: 447.942
• InChiKey: ZAUAJRUCLHZWIT-UHFFFAOYSA-N

物化性质

• 沸点：
  547.0±60.0 °C(Predicted)
• 密度：
  1.324±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 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-叔丁基-N-{6-氯-5-(3-甲氧基苯氧基)嘧啶-4-基}苯磺酰胺 生成 4-叔丁基-N-[6-(2-羟基乙氧基)-5-(3-甲氧基苯氧基)嘧啶-4-基]苯磺酰胺
  参考文献：
  名称：

  Sulfonamides

  摘要：

  化学式I的新磺胺类化合物，##STR1## 其中符号R.sup.1 -R.sup.9，R.sup.a，R.sup.b，X，Y和n的含义如描述中所示，以及其盐可用于治疗循环系统疾病，特别是高血压、缺血、血管痉挛和心绞痛。

  公开号：

  US05292740A1
• 作为产物：
  描述：

  5-(3-methoxyphenoxy)-1H-pyrimidin-4,6-dione 在 2,3,5-三甲基吡啶 、 三氯氧磷 作用下， 以 二甲基亚砜 为溶剂， 反应 4.5h， 生成 4-叔丁基-N-{6-氯-5-(3-甲氧基苯氧基)嘧啶-4-基}苯磺酰胺
  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

• Benzenesulfonamide derivative and process for preparing thereof
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US05589478A1

  公开（公告）日：1996-12-31

  A benzenesulfonamide derivative of the formula [I]: ##STR1## wherein Ring A and Ring B are the same or different and each substituted or unsubstituted benzene ring, Q is a single bond or a group of the formula: --O--, --S--, --SO--, --SO.sub.2 -- or --CH2--, Y is a group of the formula: --O--, --S-- or --NH--, Alk is lower alkylene group or lower alkenylene group, Z is a single bond or a group of the formula: --O-- or --NH--, R is a substituted or unsubstituted aromatic heterocyclic or aryl group, R.sup.1 is hydrogen atom, trifluoromethyl group, substituted or unsubstituted lower alkyl group, substituted or unsubstituted lower alkenyl group, mono-- or di-lower alkylamino group, substituted or unsubstituted lower alkylthio group, substituted or unsubstituted lower alkoxy group, substituted or unsubstituted lower alkynyl group, aromatic heterocyclic group, substituted or unsubstituted aliphatic heterocyclic group or aryl group, provided that when Z is a single bond, R is a substituted or unsubstituted aromatic heterocyclic group, or a pharmaceutically acceptable salt thereof, and processes for preparing the same, these compounds having endothelin antagonistic activity and being useful in the prophylaxis or treatment of various diseases caused by endothelin.

  一种苯磺酰胺衍生物的化学式[I]的中文翻译如下：##STR1##其中环A和环B可以相同或不同，每个都是取代或未取代的苯环，Q是一个单键或化学式的基团：--O--，--S--，--SO--，--SO.sub.2--或--CH2--，Y是化学式的基团：--O--，--S--或--NH--，Alk是较低的烷基烃基或较低的烯烃基，Z是一个单键或化学式的基团：--O--或--NH--，R是取代或未取代的芳香杂环或芳基，R.sup.1是氢原子，三氟甲基基团，取代或未取代的较低烷基基团，取代或未取代的较低烯基基团，单-或双-较低烷基氨基基团，取代或未取代的较低烷基硫基团，取代或未取代的较低烷氧基团，取代或未取代的较低炔基基团，芳香杂环基团，取代或未取代的脂环基团或芳基，但当Z是一个单键时，R是取代或未取代的芳香杂环基团，或其药学上可接受的盐，以及制备这些化合物的方法，这些化合物具有内皮素拮抗活性，并可用于预防或治疗由内皮素引起的各种疾病。
• Potent and Selective ET-A Antagonists. 1. Syntheses and Structure−Activity Relationships of <i>N</i>-(6-(2-(Aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide Derivatives
  作者：Hiroshi Morimoto、Hideshi Shimadzu、Emi Kushiyama、Hiroyuki Kawanishi、Toshihiro Hosaka、Yasushi Kawase、Kosuke Yasuda、Kohei Kikkawa、Rikako Yamauchi-Kohno、Koichiro Yamada

  DOI：10.1021/jm0102304

  日期：2001.10.1

  Modifications to the ETA/B mixed type compounds 1 (Ro. 46-2005) and 2 (bosentan) were performed. Introduction of a pyrimidine group into 1 resulted in a dramatic increase in affinity for the ETA receptor, and the subsequent optimization of substituents on the pyrimidine ring led us to the discovery of N-(6-(2-((5-bromo-2-pyrimidinyl)oxy)ethoxy)-5-(4-methylphenyl)-4pyrimidinyl)-4-tert-butylbenzenesulfonamide (7k), which showed an extremely high affinity for the human cloned ETA receptor (K-i = 0.0042 +/-0.0038 nM) and an ETA/B receptor selectivity up to 29 000 (K-i = 130 +/- 50 nM for the human cloned ETB receptor). The compound was designed on the hypothesis that the hydrogen atom of the hydroxyl group in 1 and 2 played a role not as a proton donor but as an acceptor in the possible hydrogen bonding with Tyr129. Since the incorporation of a pyrimidinyl group into the hydroxyethoxy side chain of the nonselective antagonist (1) dramatically enhanced both the ETA receptor affinity and selectivity, and since similar results were obtained from the benzene analogues, we put forward the hypothesis that a "pyrimidine binding pocket" might exist in the ETA receptor.
• Sulfonamide, ihre Herstellung und Verwendung als Heilmittel und Zwischenprodukte
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0526708B1

  公开（公告）日：2000-10-18
• US5292740A
  申请人：——

  公开号：US5292740A

  公开（公告）日：1994-03-08
• US5589478A
  申请人：——

  公开号：US5589478A

  公开（公告）日：1996-12-31