N,N'-bis(3-propionyloxy)-1,4-diazacycloheptane

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂卓
• 英文名称: N,N'-bis(3-propionyloxy)-1,4-diazacycloheptane
• 英文别名: 3,3'-(1,4-diazepane-1,4-diyl)dipropanoic acid；3-[4-(2-Carboxyethyl)-1,4-diazepan-1-yl]propanoic acid
• 化学式: C₁₁H₂₀N₂O₄
• 分子量: 244.291
• InChiKey: ZSDLKAHLMQOLPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N'-bis(3-propionyloxy)-1,4-diazacycloheptane 在 N-甲基吗啉 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.34h， 生成
  参考文献：
  名称：

  Development of New Cyclic Plasmin Inhibitors with Excellent Potency and Selectivity

  摘要：

  The trypsin-like serine protease plasmin is a target for the development of antifibrinolytic drugs for use in cardiac surgery with cardiopulmonary bypass or organ transplantations to reduce excessive blood loss. The optimization of our recently described substrate-analogue plasmin inhibitors, which were cyclized between their P3 and P2 side chains, provided a new series with improved efficacy and excellent selectivity. The most potent inhibitor 8 binds to plasmin with an inhibition constant of 0.2 nM, whereas K-i values >1 mu M were determined for nearly all other tested trypsin-like serine proteases, with the exception of trypsin, which is also inhibited in the nanomolar range. Docking studies revealed a potential binding mode in the widely open active site of plasmin that explains the strong potency and selectivity profile of these inhibitors. The dialkylated piperazine-linker segment contributes to an excellent solubility of all analogues. Based on their overall profile the presented inhibitors are well suited for further development as injectable antifibrinolytic drugs.

  DOI：

  10.1021/jm3012917
• 作为产物：
  描述：

  高哌嗪 、 3-溴丙酸 在 lithium hydroxide 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 N,N'-bis(3-propionyloxy)-1,4-diazacycloheptane
  参考文献：
  名称：

  配体设计，用于具有多种配位笼单元的独特高核CuII聚集体的碱金属模板自组装：晶体结构和性能。

  摘要：

  具有独特的四面体或八面体笼单元，[（mu（3）-Cl）[Li子集Cu（4）（mu-L（1））（3）]的两个独特的高核Cu（II）超分子聚集体的构建（3）] [ClO（4））（8）（H（2）O）（4.5）（1）和[[Na（2）子集Cu（12）（mu-L（2））（8）（ mu-Cl）（4）]（ClO（4））（8）（H（2）O）（10）（H（3）O（+））（2）]（无穷大）（2）通过碱-金属模板的（Li（+）或Na（+））自组装是通过使用两个新设计的羧基官能化的重氮杂二环配体N，N'-双（3-丙酰氧基）-1,4-二氮杂环庚烷实现的（H（2）L（1））或1,5-二氮杂环辛烷-N，N'-二乙酸（H（2）L（2））。络合物1在三角R3c空间组中结晶（a = b = 20.866（3），c = 126.26（4）A和Z = 12），在三斜晶系P1空间组中结晶2（a = 13.632（4），b = 14.754（4），c

  DOI：

  10.1002/chem.200305300

文献信息

• Ligand Design for Alkali-Metal-Templated Self-Assembly of Unique High-Nuclearity CuII Aggregates with Diverse Coordination Cage Units: Crystal Structures and Properties
  作者：Miao Du、Xian-He Bu、Ya-Mei Guo、Joan Ribas

  DOI：10.1002/chem.200305300

  日期：2004.3.19

  The construction of two unique, high-nuclearity Cu(II) supramolecular aggregates with tetrahedral or octahedral cage units, [(mu(3)-Cl)[Li subset Cu(4)(mu-L(1))(3)](3)](ClO(4))(8)(H(2)O)(4.5) (1) and [[Na(2) subset Cu(12)(mu-L(2))(8)(mu-Cl)(4)](ClO(4))(8)(H(2)O)(10)(H(3)O(+))(2)](infinity) (2) by alkali-metal-templated (Li(+) or Na(+)) self-assembly, was achieved by the use of two newly designed c

  具有独特的四面体或八面体笼单元，[（mu（3）-Cl）[Li子集Cu（4）（mu-L（1））（3）]的两个独特的高核Cu（II）超分子聚集体的构建（3）] [ClO（4））（8）（H（2）O）（4.5）（1）和[[Na（2）子集Cu（12）（mu-L（2））（8）（ mu-Cl）（4）]（ClO（4））（8）（H（2）O）（10）（H（3）O（+））（2）]（无穷大）（2）通过碱-金属模板的（Li（+）或Na（+））自组装是通过使用两个新设计的羧基官能化的重氮杂二环配体N，N'-双（3-丙酰氧基）-1,4-二氮杂环庚烷实现的（H（2）L（1））或1,5-二氮杂环辛烷-N，N'-二乙酸（H（2）L（2））。络合物1在三角R3c空间组中结晶（a = b = 20.866（3），c = 126.26（4）A和Z = 12），在三斜晶系P1空间组中结晶2（a = 13.632（4），b = 14.754（4），c
• NEW DIAMINE COMPOUND AND BRAIN PROTECTING AGENT CONTAINING THE SAME
  申请人：KOWA COMPANY LTD.

  公开号：EP0541798A1

  公开（公告）日：1993-05-19

  The present invention provides a diamine compound of formula (I) or an acid addition salt thereof: wherein R1, R2, R3, R4, R5 and R6 are the same or different from each other and represent individually a hydrogen atom, halogen atom, hydroxyl group, lower alkyl group, lower alkoxy group, lower acyloxy group, lower alkoxycarbonyloxy group, lower alkylsulfonyloxy group or am amino group, among which the lower alkyl group and lower alkoxy group may be substituted by a halogen atom or a phenyl group; R7 and R8 are the same or different from each other and represent individually a lower alkyl group or the two bind to each other to represent an alkylene group having 1 to 4 carbon atoms; A and A' are the same or different from each other and represent individually a single bond, -O-, -NH-, -NHCO→, -CONH→, -NHCOO→, NHCONH-, -SO₂NH→ or -COS→ (here, the symbol '→' denotes a bond to Y or Y'), Y and Y' are the same or different from each other and represent a lower alkylene group or lower alkenylene group; and cerebral protective drugs containing such compound. The diamine compounds (I) or its acid addition salts have an excellent cerebral protective action, are very safe, and exhibit a strong action when even orally administered, and therefore, medicines containing such compounds are effective for treating disorders caused by cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, transient ischemic attack, cerebrovascular disorders and the like, or preventing progress of such disorders.

  本发明提供了一种式 (I) 的二胺化合物或其酸加成盐： 其中 R1、R2、R3、R4、R5 和 R6 彼此相同或不同，分别代表氢原子、卤素原子、羟基、低级烷基、低级烷氧基、低级酰氧基、低级烷氧基羰氧基、低级烷基磺酰氧基或氨基，其中低级烷基和低级烷氧基可被卤素原子或苯基取代；R7 和 R8 彼此相同或不同，单独代表一个低级烷基，或两者相互结合代表一个具有 1 至 4 个碳原子的亚烷基；A和A'相同或不同，分别代表单键、-O-、-NH-、-NHCO→、-CONH→、-NHCOO→、NHCONH-、-SO₂NH→或-COS→（此处符号'→'表示与Y或Y'的键），Y和Y'相同或不同，分别代表低级亚烷基或低级亚烯基；以及含有此类化合物的脑保护药物。 二胺化合物(I)或其酸加成盐具有很好的脑保护作用，非常安全，即使口服也能表现出很强的作用，因此，含有此类化合物的药物可有效治疗由脑出血、脑梗塞、蛛网膜下腔出血、短暂性脑缺血发作、脑血管疾病等引起的疾病，或预防此类疾病的进展。
• US5389630A
  申请人：——

  公开号：US5389630A

  公开（公告）日：1995-02-14
• Development of New Cyclic Plasmin Inhibitors with Excellent Potency and Selectivity
  作者：Sebastian M. Saupe、Stephanie Leubner、Michael Betz、Gerhard Klebe、Torsten Steinmetzer

  DOI：10.1021/jm3012917

  日期：2013.2.14

  The trypsin-like serine protease plasmin is a target for the development of antifibrinolytic drugs for use in cardiac surgery with cardiopulmonary bypass or organ transplantations to reduce excessive blood loss. The optimization of our recently described substrate-analogue plasmin inhibitors, which were cyclized between their P3 and P2 side chains, provided a new series with improved efficacy and excellent selectivity. The most potent inhibitor 8 binds to plasmin with an inhibition constant of 0.2 nM, whereas K-i values >1 mu M were determined for nearly all other tested trypsin-like serine proteases, with the exception of trypsin, which is also inhibited in the nanomolar range. Docking studies revealed a potential binding mode in the widely open active site of plasmin that explains the strong potency and selectivity profile of these inhibitors. The dialkylated piperazine-linker segment contributes to an excellent solubility of all analogues. Based on their overall profile the presented inhibitors are well suited for further development as injectable antifibrinolytic drugs.