4-[4-[{N-methyl-N-(pyrimidin-2-yl)}amino]piperidin-1-yl]benzoic acid | 247035-15-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-[4-[{N-methyl-N-(pyrimidin-2-yl)}amino]piperidin-1-yl]benzoic acid
• 英文别名: 4-[4-[Methyl(pyrimidin-2-yl)amino]piperidin-1-yl]benzoic acid
• CAS: 247035-15-0
• 化学式: C₁₇H₂₀N₄O₂
• 分子量: 312.371
• InChiKey: HMXBRURXBQYVRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[4-[{N-methyl-N-(pyrimidin-2-yl)}amino]piperidin-1-yl]benzoic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 (2S)-benzenesulfonylamino-3-[4-[4-[{N-methyl-N-(pyrimidin-2-yl)}amino]piperidin-1-yl]benzoylamino]propionic acid
  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：

  对氟苯甲酸乙酯 在 sodium hydroxide 、 三丁基膦 、 sodium hydride 、 一水合肼 、 N,N-二异丙基乙胺 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 甲醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 137.0h， 生成 4-[4-[{N-methyl-N-(pyrimidin-2-yl)}amino]piperidin-1-yl]benzoic acid
  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

• AMINOPIPERIDINE DERIVATIVES AS INTEGRIN ALPHA V BETA 3 ANTAGONISTS
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP1074543A1

  公开（公告）日：2001-02-07

  Compounds having integrin αvβ3 antagonism, cell adhesion inhibitory effect, GP IIb/IIIa antagonism and/or human platelet agglutination inhibitory effect; and remedies for cardiovascular diseases, diseases in association with neovascularization, cerebrovascular diseases, etc. and platelet agglutination inhibitors. The above compounds involve derivatives represented by general formula (I), pharmaceutically acceptable salts thereof and solvates of the same, wherein A represents a 5- to 7-membered heterocycle containing two nitrogen atoms; D represents >NH2, >CH2, etc.; X and Z represent each CH or N; R7 and R8 represent each alkyl, halogeno, etc.; Q represents >C=O, >CH2, etc.; R9 represents H, alkyl, aralkyl, etc.; R10 represents H, alkynyl, etc.; R11 represents H, substituted amino, etc.; R12 represents H or alkyl; m is from 0 to 5; n is from 0 to 4; p and q are each from 1 to 3; and r is 0 or 1.

  具有整合素αvβ3拮抗作用、细胞粘附抑制作用、GPⅡb/Ⅲa拮抗作用和/或人体血小板凝集抑制作用的化合物；以及治疗心血管疾病、与新生血管有关的疾病、脑血管疾病等的药物和血小板凝集抑制剂。上述化合物涉及通式（I）代表的衍生物、其药学上可接受的盐及其溶液，其中 A 代表含有两个氮原子的 5 至 7 元杂环；D 代表 >NH2、>CH2 等。X和Z分别代表CH或N；R7和R8分别代表烷基、卤代等；Q代表>C=O、>CH2等；R9代表H、烷基、芳烷基等；R10代表H、炔基等；R11代表H、取代氨基等；R12代表H或烷基；m为0至5；n为0至4；p和q分别为1至3；r为0或1。
• US6420558B1
  申请人：——

  公开号：US6420558B1

  公开（公告）日：2002-07-16
• 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.