4,6-dichloro-5-(2-methoxyphenoxy)-2-cyclopropyl-pyrimidine | 329924-27-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4,6-dichloro-5-(2-methoxyphenoxy)-2-cyclopropyl-pyrimidine
• 英文别名: 4,6-dichloro-2-cyclopropyl-5-(2-methoxy-phenoxy)pyrimidine；4,6-dichloro-2-cyclopropyl-5-(o-methoxyphenoxy)-pyrimidine；4,6-dichloro-2-cyclopropyl-5-(2-methoxyphenoxy)pyrimidine
• CAS: 329924-27-8
• 化学式: C₁₄H₁₂Cl₂N₂O₂
• 分子量: 311.167
• InChiKey: JVYKFTSRHBWVPQ-UHFFFAOYSA-N

物化性质

• 沸点：
  386.6±42.0 °C(Predicted)
• 密度：
  1.399±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,6-dichloro-5-(2-methoxyphenoxy)-2-cyclopropyl-pyrimidine 在 4-二甲氨基吡啶 、 sodium 作用下， 以 甲苯 为溶剂， 生成 pyridin-2-ylcarbamic acid 2-[6-(4-tert-butyl-phenylsulfonylamino)-2-cyclopropyl-5-(2-methoxy-phenoxy)-pyrimidin-4-yloxy]-ethyl ester
  参考文献：
  名称：

  Discovery of Ro 48-5695: A potent mixed endothelin receptor antagonist optimized from bosentan

  摘要：

  Implementation of a pyridylcarbamoyl group and an isopropylpyridylsulfonamide substituent as key components in the scaffold of Bosentan resulted in the identification of the potent orally active endothelin receptor antagonist Ro 48-5695. It shows affinities for ETA and ETB receptors in the low nanomolar range and high functional antagonistic potency in vitro. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00400-9
• 作为产物：
  描述：

  2-甲氧基苯氧乙酸 在 氯化亚砜 、 sodium 、 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基苯胺 、 mineral oil 为溶剂， 反应 56.0h， 生成 4,6-dichloro-5-(2-methoxyphenoxy)-2-cyclopropyl-pyrimidine
  参考文献：
  名称：

  的发现ñ - [5-（4-溴苯基）-6- [2 - [（5-溴-2-嘧啶基）氧基]乙氧基] -4-嘧啶基] - ñ '-propylsulfamide（美西特田），一种口服活性，强效双重内皮素受体拮抗剂

  摘要：

  从波生坦（1）的结构开始，我们着手于一项药物化学程序，旨在鉴定具有高口服功效的新型有效的双重内皮素受体拮抗剂。这导致发现了一系列新的烷基磺酰胺取代的嘧啶。其中，化合物17（macitentan，ACT-064992）引起了人们的特别关注，因为它是对ET B受体具有显着亲和力的ET A的有效抑制剂，并且在高血压Dahl盐敏感性大鼠中显示出优异的药代动力学特性和高体内功效。化合物17成功完成了一项肺动脉高压的长期III期临床试验。

  DOI：

  10.1021/jm3009103

文献信息

• Novel sulfamides and their use as endothelin receptor antagonists
  申请人：——

  公开号：US20040077670A1

  公开（公告）日：2004-04-22

  The invention relates to novel sulfamides 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.

  本发明涉及新型磺酰胺及其在制备药物组合物中作为活性成分的应用。该发明还涉及相关方面，包括化合物的制备过程、含有其中一种或多种化合物的药物组合物，以及它们作为内皮素受体拮抗剂的应用。
• [EN] NOVEL SULFAMIDES AND THEIR USE AS ENDOTHELIN RECEPTOR ANTAGONISTS<br/>[FR] NOUVEAUX SULFAMIDES ET LEUR UTILISATION COMME ANTAGONISTES DU RECEPTEUR DE L'ENDOTHELINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2002053557A1

  公开（公告）日：2002-07-11

  The invention relates to novel sulfamides of general formula (I) 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.

  本发明涉及一种新型一般式（I）的磺胺类化合物，以及它们在制备药物组合物的活性成分中的应用。本发明还涉及相关方面，包括化合物的制备过程，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。
• Novel sulfamides
  申请人：Bolli Martin

  公开号：US20060178365A1

  公开（公告）日：2006-08-10

  The invention relates to novel sulfamides 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.

  本发明涉及新型磺酰胺及其在制备药物组合物中作为活性成分的用途。本发明还涉及相关方面，包括合成这些化合物的过程、含有这些化合物中的一个或多个的药物组合物，特别是它们作为内皮素受体拮抗剂的用途。
• 6 alkoxy-4-pyrimidinyl bis-sulfonamides
  申请人：Actelio Pharmaceuticals Ltd.

  公开号：US06596719B1

  公开（公告）日：2003-07-22

  The present invention relates to novel bis-sulfonamides represented, for example, by formula I below and a pure diastereomer, a mixture of diastereomers, a diastereomeric racemate, a mixture of diastereomeric racemates and meso-forms and a pharmaceutically acceptable salt thereof, wherein R1 represents aryl; aryl-lower alkyl; aryl-lower alkenyl; heteroaryl; or heteroaryl-lower alkyl; and R2 represents lower alkyl; trifluoromethyl; lower alkoxy-lower alkyl; lower alkenyl; lower alkynyl; aryl; aryl-lower alkyl; aryl-lower alkenyl; heterocyclyl; heterocyclyl-lower alkyl; heteroaryl; heteroaryl-lower alkyl; cycloalkyl; or cycloalkyl-lower alkyl. The present invention also relates to a process for manufacturing those compounds, pharmaceutical compositions containing one or more of those compounds as endothelin antagonists, and a method of treating a subject having a disorder involving endothelin with the compounds of the invention.

  本发明涉及一种新型双磺酰胺，例如以下式I所示的双磺酰胺及其纯对映异构体、对映异构体混合物、对映异构体外消旋体混合物和中间体形式以及其药学上可接受的盐，其中R1代表芳基；芳基-较低烷基；芳基-较低烯基；杂环芳基；或杂环芳基-较低烷基；R2代表较低烷基；三氟甲基；较低烷氧-较低烷基；较低烯基；较低炔基；芳基；芳基-较低烷基；芳基-较低烯基；杂环基；杂环基-较低烷基；杂环芳基；杂环芳基-较低烷基；环烷基；或环烷基-较低烷基。本发明还涉及一种制造这些化合物的方法，以及含有该化合物作为内皮素拮抗剂的制药组合物和使用本发明化合物治疗涉及内皮素的疾病的方法。
• Novel Sulfamides and their use as endothelin receptor antagonists
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP1693372A1

  公开（公告）日：2006-08-23

  The invention relates to novel sulfamides of the general formula (I) 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.

  本发明涉及通式（I）的新型氨基磺酸盐及其在制备药物组合物中作为活性成分的用途。本发明还涉及相关方面，包括制备这些化合物的工艺、含有一种或多种这些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。