1-(4-nitrophenyl)-4-(pyridin-4-yl)-1,4-diazepane | 220220-06-4

• 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: 1-(4-nitrophenyl)-4-(pyridin-4-yl)-1,4-diazepane
• 英文别名: 1-(4-nitrophenyl)-4-(pyridin-4-yl)hexahydro-1H-1,4-diazepine；1-(4-nitrophenyl)-4-(4-pyridyl)hexahydro-1H-1,4-diazepine；1-(4-Nitrophenyl)-4-pyridin-4-yl-1,4-diazepane
• CAS: 220220-06-4
• 化学式: C₁₆H₁₈N₄O₂
• 分子量: 298.345
• InChiKey: MKGDJWPFEFVRDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-nitrophenyl)-4-(pyridin-4-yl)-1,4-diazepane 在 palladium on activated charcoal 氢气 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 21.0h， 生成 7-[({4-[4-(pyridin-4-yl)-1,4-diazepan-1-yl]phenyl}amino)methyl]-2-naphthonitrile
  参考文献：
  名称：

  Synthesis and biological activity of novel 1,4-diazepane derivatives as factor Xa inhibitor with potent anticoagulant and antithrombotic activity

  摘要：

  Factor Xa (fXa) is a serine protease involved in the coagulation cascade, which has received great interest as a potential target for the development of new antithrombotic drugs. Herein we report a novel series of fXa inhibitors in which the 1,4-diazepane moiety was designed to interact with the S4 aryl-binding domain of the fXa active site. Compound 13 (YM-96765) showed potent fXa inhibitory activity (IC50 = 6.8 nM) and effective antithrombotic activity without prolonging bleeding time. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.022
• 作为产物：
  描述：

  对氟硝基苯 、 1-(pyridin-4-yl)-1,4-diazepane 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 以54%的产率得到1-(4-nitrophenyl)-4-(pyridin-4-yl)-1,4-diazepane
  参考文献：
  名称：

  Synthesis and biological activity of novel 1,4-diazepane derivatives as factor Xa inhibitor with potent anticoagulant and antithrombotic activity

  摘要：

  Factor Xa (fXa) is a serine protease involved in the coagulation cascade, which has received great interest as a potential target for the development of new antithrombotic drugs. Herein we report a novel series of fXa inhibitors in which the 1,4-diazepane moiety was designed to interact with the S4 aryl-binding domain of the fXa active site. Compound 13 (YM-96765) showed potent fXa inhibitory activity (IC50 = 6.8 nM) and effective antithrombotic activity without prolonging bleeding time. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.022

文献信息

• Hexahydro-1,4-diazepine derivatives or salts thereof
  申请人：Yamanouchi Pharmaceutical Co.

  公开号：US06333320B1

  公开（公告）日：2001-12-25

  Hexahydro-1,4-diazepine derivatives represented by general formula (I); pharmaceutically acceptable salts thereof; and drugs containing the same as the active ingredient, such as activated blood coagulation factor X inhibitor, wherein A: phenylene, pyridylene, or the like; B: a 5- or 6-membered aryl or heteroaryl ring; X: —CO—, —CONH—, —CSNH—, —SO2—, —SO2NH—, or the like; Y: a bond or alkylene; R1: hydrogen, alkyl, —Y—(hetero) aryl, or the like; R2: hydrogen, alkoxy, —COOH, or the like; R3: amidino or a group capable of being converted into amidino; and R4, R5: each independently hydrogen or lower alkyl.

  一般式（I）所代表的六氢-1,4-二氮杂环衍生物；其药学上可接受的盐；以及包含其作为活性成分的药物，例如激活的血凝血因子X抑制剂，其中A：苯撑基，吡啶撑基或类似物；B：5-或6-成员芳基或杂芳基环；X：-CO-，-CONH-，-CSNH-，-SO2-，-SO2NH-或类似物；Y：键或烷基；R1：氢，烷基，-Y-（杂）芳基或类似物；R2：氢，烷氧基，-COOH或类似物；R3：酰胺基或可转化为酰胺基的基团；以及R4，R5：各自独立地为氢或低级烷基。
• NOVEL HEXAHYDRO-1,4-DIAZEPINE DERIVATIVES OR SALTS THEREOF
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP1000936A1

  公开（公告）日：2000-05-17

  Hexahydro-1,4-diazepine derivatives represented by general formula (I); pharmaceutically acceptable salts thereof; and drugs containing the same as the active ingredient, such as activated blood coagulation factor X inhibitor, wherein A: phenylene, pyridylene, or the like; B: a 5- or 6-membered aryl or heteroaryl ring; X: -CO-, -CONH-, -CSNH-, -SO2-, -SO2NH-, or the like; Y: a bond or alkylene; R1: hydrogen, alkyl, -Y-(hetero)aryl, or the like; R2: hydrogen, alkoxy, -COOH, or the like; R3: amidino or a group capable of being converted into amidino; and R4, R5: each independently hydrogen or lower alkyl.

  由通式(I)代表的六氢-1,4-二氮杂卓衍生物；其药学上可接受的盐；以及以其为活性成分的药物，如活化凝血因子 X 抑制剂，其中 A：亚苯基、亚吡啶基或类似物；B：5 或 6 元芳基或杂芳基环；X：-CO-、-CONH-、-CSNH-、-SO2-、-SO2NH- 或类似物； Y：键或亚烷基； R1：氢、烷基、-Y-（杂）芳基或类似物； R2：氢、烷氧基、-COOH 或类似物； R3：脒基或可转化为脒基的基团；以及 R4、R5：各自独立的氢或低级烷基。
• US6333320B1
  申请人：——

  公开号：US6333320B1

  公开（公告）日：2001-12-25
• Synthesis and biological activity of novel 1,4-diazepane derivatives as factor Xa inhibitor with potent anticoagulant and antithrombotic activity
  作者：Hiroyuki Koshio、Fukushi Hirayama、Tsukasa Ishihara、Yuta Taniuchi、Kazuo Sato、Yumiko Sakai-Moritani、Seiji Kaku、Tomihisa Kawasaki、Yuzo Matsumoto、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1016/j.bmc.2004.02.022

  日期：2004.5

  Factor Xa (fXa) is a serine protease involved in the coagulation cascade, which has received great interest as a potential target for the development of new antithrombotic drugs. Herein we report a novel series of fXa inhibitors in which the 1,4-diazepane moiety was designed to interact with the S4 aryl-binding domain of the fXa active site. Compound 13 (YM-96765) showed potent fXa inhibitory activity (IC50 = 6.8 nM) and effective antithrombotic activity without prolonging bleeding time. (C) 2004 Elsevier Ltd. All rights reserved.