N-[6-{2-(5-Bromopyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide | 169677-30-9

• 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: N-[6-{2-(5-Bromopyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide
• 英文别名: 4-tert-butyl-N-{6-[2-(5-bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide；N-[6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-5-(4-methylphenyl)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide
• CAS: 169677-30-9
• 化学式: C₂₇H₂₈BrN₅O₄S
• 分子量: 598.52
• InChiKey: XCDYCRJUBJSYLD-UHFFFAOYSA-N

物化性质

• 熔点：
  167-168 °C
• 沸点：
  713.3±70.0 °C(Predicted)
• 密度：
  1.408±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 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：

  N-[6-{2-(5-Bromopyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide 在 sodium tetrahydroborate 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 异丙醇 为溶剂， 反应 2.5h， 生成 4-tert-butyl-N-[6-{2-(5-hydroxymethylpyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]benzenesulfonamide
  参考文献：
  名称：

  有力和选择性的ET-A拮抗剂。2.发现和评价有效和水溶性的N-（6-（2-（芳氧基）乙氧基）-4-嘧啶基）磺酰胺衍生物。

  摘要：

  在上一篇文章中，（1）我们概述了有效的选择性ET（A）受体拮抗剂1及其相关化合物的发现及其与构效关系。鉴定出具有有效的选择性ET（A）受体拮抗剂活性的1的代谢物。这项研究表明1的代谢途径受物种的影响很大。因此，进行了结构修饰1以改善代谢途径的复杂性和水溶性。随后在1的叔丁基部分引入羟基导致了我们新的临床候选物6b的发现，该候选物显示出更高的水溶性，物种间统一的代谢途径以及对人类的极高亲和力和选择性ET（A）受体（ET（A）受体的K（i）：0.015 +/- 0.004 nM; ET（B）受体的K（i）：41 +/- 21 nM）。

  DOI：

  10.1021/jm000538f
• 作为产物：
  描述：

  5-溴-2-氯嘧啶 、 p-tert-butyl-N-[6-(2-hydroxyethoxy)-5-p-tolyl-4-pyrimidinyl]benzenesulfonamide 在 sodium hydride 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 7.33h， 以88%的产率得到N-[6-{2-(5-Bromopyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide
  参考文献：
  名称：

  Potent and Selective ET-A Antagonists. 1. Syntheses and Structure−Activity Relationships of N-(6-(2-(Aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide Derivatives

  摘要：

  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.

  DOI：

  10.1021/jm0102304

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。
• Enzymatic oxidations
  申请人：——

  公开号：US20020012977A1

  公开（公告）日：2002-01-31

  The following invention relates to a process for oxidizing alkyl groups attached directly or via a linker, to a sulfonamide moiety (II) by the use of cytochrome P450 enzymes, to give the corresponding alcohol or carboxylic acid (I). 1 wherein R is an organic radical, X is a linker, Y is —C(CH 3 ) 2 — or —CH(CH 3 )— and Z is —CH 2 OH or —COOH.

  以下发明涉及一种使用细胞色素P450酶氧化直接或通过连接剂连接的烷基基团至磺酰胺基团(II)的过程，以得到相应的醇或羧酸(I)。其中，R为有机基团，X为连接剂，Y为—C(CH3)2—或—CH(CH3)—，Z为—CH2OH或—COOH。
• METHOD AND COMPOSITION FOR TREATING DIABETIC KETOACIDOSIS
  申请人：Midwestern University

  公开号：EP2424530B1

  公开（公告）日：2015-12-16
• Method and Composition for Potentiating the Antipyretic Action of a Nonopiod Analgesic
  申请人：Gulati Anil

  公开号：US20080207763A1

  公开（公告）日：2008-08-28

  A composition and method of treating fever, and optionally treating pain, is disclosed. The composition and method utilize a nonopioid analgesic and an endothelin antagonist as active agents to treat fever in mammals, including humans. The composition also is useful in the prevention and treatment of stroke and other cardiovascular disorders, like myocardial infarction.
• Diagnostic Use of Endothelin Etb Receptor Agonists and Eta Receptor Antagonists in Tumor Imaging
  申请人：Gulati Anil

  公开号：US20080260634A1

  公开（公告）日：2008-10-23

  Methods of imaging tumors are disclosed. The methods utilize an endothelin ET B receptor agonist or an endothelin ET A receptor antagonist, in combination with an imaging agent, to detect a tumor in mammals, including humans.