4-amino-6-(2-hydroxyethoxy)-5-(4-methylphenyl)pyrimidine | 169677-36-5

• 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: 4-amino-6-(2-hydroxyethoxy)-5-(4-methylphenyl)pyrimidine
• 英文别名: 2-{6-amino-5-(4-methylphenyl)pyrimidin-4-yloxy}ethanol；2-[6-amino-5-(4-methylphenyl)pyrimidin-4-yl]oxyethanol
• CAS: 169677-36-5
• 化学式: C₁₃H₁₅N₃O₂
• 分子量: 245.281
• InChiKey: VYBWOLREYOQAKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  81.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-amino-6-(2-hydroxyethoxy)-5-(4-methylphenyl)pyrimidine 在 氢氧化钾 、 四丁基硫酸氢铵 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 32.08h， 生成 N-{6-[2-(5-Bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)-pyrimidin-4-yl}naphthalenesulfonamide
  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
• 作为产物：
  描述：

  4-chloro-6-(2-hydroxyethoxy)-5-(4-methylphenyl)pyrimidine 在 10percent Pd/C sodium azide 、 水 、 氢气 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 4-amino-6-(2-hydroxyethoxy)-5-(4-methylphenyl)pyrimidine
  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

• Arylalkane-sulfonamides having endothelin-antagonist activity
  申请人：——

  公开号：US20040102464A1

  公开（公告）日：2004-05-27

  The invention relates to novel aryl-alkane-sulfonamides and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.

  这项发明涉及新型芳基-烷基-磺酰胺及其在制备药物组合物中作为活性成分的用途。该发明还涉及相关方面，包括制备这些化合物的过程、含有其中一种或多种化合物的药物组合物，特别是它们作为内皮素受体拮抗剂的用途。
• 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。
• Sulfonamide derivative and process for preparing the same
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US05739333A1

  公开（公告）日：1998-04-14

  Novel sulfonamide derivatives of the formula \x9bI!: ##STR1## wherein Ring A and Ring B are substituted or unsubstituted monocyclic, bicyclic or tricyclic hydrocarbon, or substituted or unsubstituted heterocyclic group, Q is single bond, --O--, --S--, --SO--, --SO.sub.2 -- or --CH.sub.2 --, Y is --0--, --S-- or --NH--, Alk is lower alkylene or alkenylene, Z is --O-- or --NH --, R is substituted or unsubstituted aromatic heterocyclic or aryl, R.sup.1 is H, substituted or unsubstituted amino, substituted or unsubstituted lower alkyl, alkenyl, alkynyl, substituted or unsubstituted lower alkylthio, or alkoxy, or substituted or unsubstituted heterocyclic or aryl, or pharmaceutically acceptable salts thereof, which are useful in the prophylaxis or treatment of disorders associated with endothelin activities such as hypertension, pulmonary hypertension, renal hypertension, Raynaud disease, bronchial asthma, gastric ulcer, chronic heart failure, etc.

  新型磺胺衍生物的化学式如下：##STR1##其中环A和环B是取代或未取代的单环、双环或三环碳氢化合物，或取代或未取代的杂环基团，Q是单键，-O-，-S-，-SO-，-SO.sub.2-或-CH.sub.2-，Y是-0-，-S-或-NH-，Alk是较低的烷基或烯基，Z是-O-或-NH-，R是取代或未取代的芳香杂环或芳基，R.sup.1是H，取代或未取代的氨基，取代或未取代的较低烷基、烯基、炔基、取代或未取代的较低烷硫基或烷氧基，或取代或未取代的杂环基团或芳基，或其药用盐，这些化合物在预防或治疗与内皮素活性相关的疾病方面具有用途，如高血压、肺动脉高压、肾高血压、雷诺病、支气管哮喘、胃溃疡、慢性心力衰竭等。
• Novel arylethene-sulfonamides
  申请人：——

  公开号：US20030220359A1

  公开（公告）日：2003-11-27

  The invention relates to novel aryl-ethene-sulfonamides and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.

  这项发明涉及新颖的芳基乙烯磺酰胺及其在制备药物组合物中作为活性成分的用途。该发明还涉及相关方面，包括制备这些化合物的过程、含有其中一个或多个化合物的药物组合物，特别是它们作为内皮素受体拮抗剂的用途。
• Novel alkansulfonamides as endothelin antagonists
  申请人：Bolli Martin

  公开号：US20050085639A1

  公开（公告）日：2005-04-21

  The invention relates to novel alkansulfonamides of structure (I), wherein R 1 is a lowel alzyl group and the other variables are as defined in the description, and their use as active ingredients in the preparation of pharmaceutical compositions. The invention aslo concerns related aspects inluding processes for the preparation of the compounds, pharmaccutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists in the treatment and prevention of diseases associated to the endothelin system.

  本发明涉及结构式(I)的新型烷基磺酰胺，其中R1是低碳基烷基，其他变量如描述中所定义，并且它们在制备药物组成中的活性成分中的使用。本发明还涉及相关方面，包括制备化合物的方法，含有这些化合物中的一个或多个的药物组成物，尤其是它们作为内皮素受体拮抗剂在治疗和预防与内皮素系统相关的疾病方面的使用。