ethyl 4-{4-(pyrimidin-2-yl)-[1,4]diazepan-1-yl}benzoate | 234081-77-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-{4-(pyrimidin-2-yl)-[1,4]diazepan-1-yl}benzoate
• 英文别名: ethyl 4-{4-(pyrimidin-2-yl)-[1,4]diazepan-1-yl}-benzoate；Ethyl 4-[hexahydro-4-(2-pyrimidinyl)-1H-1,4-diazepin-1-yl]benzoate；ethyl 4-(4-pyrimidin-2-yl-1,4-diazepan-1-yl)benzoate
• CAS: 234081-77-7
• 化学式: C₁₈H₂₂N₄O₂
• 分子量: 326.398
• InChiKey: LVXJGBVALMLGEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-{4-(pyrimidin-2-yl)-[1,4]diazepan-1-yl}benzoate 在 N-甲基吗啉 、 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 tert-butyl (2S)-benzenesulfonylamino-3-[4-{4-(pyrimidin-2-yl)-[1,4]diazepan-1-yl}benzoylamino]propionate
  参考文献：
  名称：

  Tricyclic pharmacophore-based molecules as novel integrin αvβ3 antagonists. Part 1: Design and synthesis of a lead compound exhibiting αvβ3/αIIbβ3 dual antagonistic activity

  摘要：

  In order to generate novel compounds with integrin alpha(v)beta(3)-antagonistic activity together with antiplatelet activity, tricyclic pharmacophore-based molecules were designed and synthesized. Although piperazine-containing compounds initially prepared were selective alpha(IIb)beta(3) antagonists, replacement of piperazine with piperidine furnished a potent alpha(v)beta(3)/alpha(IIb)beta(3) dual antagonist. Structureactivity relationship (SAR) studies provided clues for further development of tricyclic pharmacophore-based integrin antagonists. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.060
• 作为产物：
  描述：

  高哌嗪 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 ethyl 4-{4-(pyrimidin-2-yl)-[1,4]diazepan-1-yl}benzoate
  参考文献：
  名称：

  Tricyclic pharmacophore-based molecules as novel integrin αvβ3 antagonists. Part 1: Design and synthesis of a lead compound exhibiting αvβ3/αIIbβ3 dual antagonistic activity

  摘要：

  In order to generate novel compounds with integrin alpha(v)beta(3)-antagonistic activity together with antiplatelet activity, tricyclic pharmacophore-based molecules were designed and synthesized. Although piperazine-containing compounds initially prepared were selective alpha(IIb)beta(3) antagonists, replacement of piperazine with piperidine furnished a potent alpha(v)beta(3)/alpha(IIb)beta(3) dual antagonist. Structureactivity relationship (SAR) studies provided clues for further development of tricyclic pharmacophore-based integrin antagonists. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.060

文献信息

• PHENYLPIPERAZINE DERIVATIVES AS INTEGRIN ALPHAvBETA3 ANTAGONISTS
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP1057818A1

  公开（公告）日：2000-12-06

  An objective of the present invention is to provide compounds having integrin αvβ3 antagonistic activity, GP IIb/IIIa antagonistic activity, and/or human platelet aggregation inhibitory activity, and therapeutic agents for treating integrin αvβ3-mediated diseases and for inhibiting platelet aggregation. The derivatives according to the present invention are compounds represented by formula (I) or pharmaceutically acceptable salts or solvates thereof: wherein A represents a five- to seven-membered heterocyclic ring containing two nitrogen atoms or the like; X and Z represent CH or a nitrogen atom; R4 and R5 represent alkyl, halogen or the like; Q represents >C=O, >CH2 or the like; R6 represents H, alkyl, aralkyl or the like; R7 represents H, alkynyl or the like; R8 represents H, substituted amino or the like; R9 represents H or alkyl; m is 0 to 5; n is 0 to 4; p is 2 or 3; and q is 0 or 1.

  本发明的目的是提供具有整合素αvβ3拮抗活性、GPⅡb/Ⅲa拮抗活性和/或人体血小板聚集抑制活性的化合物，以及治疗整合素αvβ3介导的疾病和抑制血小板聚集的治疗剂。根据本发明的衍生物是式 (I) 所代表的化合物或其药学上可接受的盐或溶液： 其中 A 代表含有两个氮原子或类似物的五至七元杂环；X 和 Z 代表 CH 或氮原子；R4 和 R5 代表烷基、卤素或类似物；Q 代表 >C=O、>CH2 或类似物；R6 代表 H、烷基、芳烷基或类似物；R7 代表 H、炔基或类似物；R8 代表 H、取代氨基或类似物；R9 代表 H 或烷基；m 为 0 至 5；n 为 0 至 4；p 为 2 或 3；q 为 0 或 1。
• US6451800B1
  申请人：——

  公开号：US6451800B1

  公开（公告）日：2002-09-17
• Tricyclic pharmacophore-based molecules as novel integrin αvβ3 antagonists. Part 1: Design and synthesis of a lead compound exhibiting αvβ3/αIIbβ3 dual antagonistic activity
  作者：Dai Kubota、Minoru Ishikawa、Mikio Yamamoto、Shoichi Murakami、Mitsugu Hachisu、Kiyoaki Katano、Keiichi Ajito

  DOI：10.1016/j.bmc.2005.10.060

  日期：2006.4

  In order to generate novel compounds with integrin alpha(v)beta(3)-antagonistic activity together with antiplatelet activity, tricyclic pharmacophore-based molecules were designed and synthesized. Although piperazine-containing compounds initially prepared were selective alpha(IIb)beta(3) antagonists, replacement of piperazine with piperidine furnished a potent alpha(v)beta(3)/alpha(IIb)beta(3) dual antagonist. Structureactivity relationship (SAR) studies provided clues for further development of tricyclic pharmacophore-based integrin antagonists. (c) 2005 Elsevier Ltd. All rights reserved.