4-{4-(Pyrimidin-2-yl)-piperazin-1-yl}-benzoic acid | 234081-73-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-{4-(Pyrimidin-2-yl)-piperazin-1-yl}-benzoic acid
• 英文别名: 4-{4-(Pyrimidin-2-yl)piperazin-1-yl}benzoic acid；4-(4-pyrimidin-2-ylpiperazin-1-yl)benzoic acid
• CAS: 234081-73-3
• 化学式: C₁₅H₁₆N₄O₂
• 分子量: 284.318
• InChiKey: NRBRIGNDIHMXTE-UHFFFAOYSA-N

物化性质

• 沸点：
  551.3±60.0 °C(Predicted)
• 密度：
  1.316±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 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-(Pyrimidin-2-yl)-piperazin-1-yl}-benzoic acid 在 palladium on activated charcoal N-甲基吗啉 、 盐酸 、 氢气 、 1-羟基苯并三唑 、 溶剂黄146 、 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， 20.0 ℃ 、303.98 kPa 条件下， 反应 33.0h， 生成 (2S)-amino-3-[4-{4-(1,4,5,6-tetrahydropyrimidin-2-yl)-piperazin-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：

  4-(1-哌嗪基)苯甲酸乙酯 在 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 4-{4-(Pyrimidin-2-yl)-piperazin-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

• &OHgr;-amino-&agr;-hydroxycarboxylic acid derivatives having integrin &agr;&ngr;&bgr;3 antagonistic activity
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：US06750219B1

  公开（公告）日：2004-06-15

  An objective of the present invention is to provide highly water-soluble compounds having integrin &agr;v&bgr;3 antagonistic activity. The compounds according to the present invention are compounds represented by formula (I) and pharmaceutically acceptable salts or solvates thereof: wherein A represents a two nitrogen atom-containing optionally substituted saturated or unsaturated five- to seven-membered heterocyclic group, which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a bicyclic group, or —C(—NR1R2)(═NR3) wherein R1, R2, and R3 represent hydrogen, alkyl or the like; D represents a bond, >NR4, wherein R4 represents hydrogen or optionally substituted alkyl, —O—, or —S—; X and Z represent either CH or N; R7 and R8 represent C1-6 alkyl, halogen, oxygen or the like; Q represents >C═O, >CHR13 or >CHOR13 wherein R13 represents hydrogen or alkyl; R9 represents hydrogen, alkyl or the like; J represents a bond or alkylene having 1 to 3 carbon atoms; R10 and R11 represent hydrogen, alkyl or the like; m is an integer of 0 to 5; n is an integer of 0 to 4; and p and q are an integer of 1 to 3.

  本发明的目标是提供高度水溶性的化合物，具有整合素αvβ3拮抗活性。根据本发明的化合物是由式(I)及其药学上可接受的盐或溶剂表示的化合物：其中A代表含有两个氮原子的可选取代的饱和或不饱和的五到七元杂环基团，该基团可选地与另一个碳环或杂环环并形成双环基团，或-C（-NR1R2）（═ NR3）其中R1、R2和R3代表氢、烷基或类似物；D代表键，>NR4，其中R4代表氢或可选取代的烷基，-O-或-S-;X和Z代表CH或N;R7和R8代表C1-6烷基、卤素、氧或类似物；Q代表>C═O，>CHR13或>CHOR13，其中R13代表氢或烷基；R9代表氢、烷基或类似物；J代表键或具有1至3个碳原子的烷基；R10和R11代表氢、烷基或类似物；m是0至5的整数；n是0至4的整数；p和q是1至3的整数。
• 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。
• OMEGA-AMINO-ALPHA-HYDROXYCARBOXYLIC ACID DERIVATIVES HAVING INTEGRIN ALPHA V BETA 3 ANTAGONISM
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP1209152A1

  公开（公告）日：2002-05-29

  An objective of the present invention is to provide highly water-soluble compounds having integrin ανβ3 antagonistic activity. The compounds according to the present invention are compounds represented by formula (I) and pharmaceutically acceptable salts or solvates thereof: wherein A represents a two nitrogen atom-containing optionally substituted saturated or unsaturated five- to seven-membered heterocyclic group, which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a bicyclic group, or C(-NR1R2)(=NR3) wherein R1, R2, and R3 represent hydrogen, alkyl or the like; D represents a bond, >NR4, wherein R4 represents hydrogen or optionally substituted alkyl, -O-, or -S-; X and Z represent either CH or N; R7 and R8 represent C1-6 alkyl, halogen, oxygen or the like; Q represents >C=O, >CHR13 or >CHOR13 wherein R13 represents hydrogen or alkyl; R9 represents hydrogen, alkyl or the like; J represents a bond or alkylene having 1 to 3 carbon atoms; R10 and R11 represent hydrogen, alkyl or the like; m is an integer of 0 to 5; n is an integer of 0 to 4; and p and q are an integer of 1 to 3.

  本发明的目的是提供具有整合素ανβ3拮抗活性的高水溶性化合物。根据本发明的化合物是式 (I) 所代表的化合物及其药学上可接受的盐或溶液： 其中 A 代表含两个氮原子的任选取代的饱和或不饱和的五至七元杂环基团，该杂环基团可任选与另一个碳环或杂环缩合形成双环基团，或 C(-NR1R2)(=NR3)，其中 R1、R2 和 R3 代表氢、烷基或类似物；D 代表键，>NR4，其中 R4 代表氢或任选取代的烷基、-O- 或 -S-；X 和 Z 代表 CH 或 N；R7 和 R8 代表 C1-6 烷基、卤素、氧或类似物；Q 代表 >C=O、>CHR13 或 >CHOR13，其中 R13 代表氢或烷基；R9 代表氢、烷基或类似物；J 代表键或具有 1 至 3 个碳原子的亚烷基；R10 和 R11 代表氢、烷基或类似物；m 是 0 至 5 的整数；n 是 0 至 4 的整数；p 和 q 是 1 至 3 的整数。
• US6451800B1
  申请人：——

  公开号：US6451800B1

  公开（公告）日：2002-09-17
• US6750219B1
  申请人：——

  公开号：US6750219B1

  公开（公告）日：2004-06-15