4,4'-pentamethylenedioxydibenzamideoxime

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4,4'-pentamethylenedioxydibenzamideoxime
• 英文别名: pentamidine bis(amidoxime)；pentamidine diamidoxime；pentamidine DAO；N'-hydroxy-4-[5-[4-[(Z)-N'-hydroxycarbamimidoyl]phenoxy]pentoxy]benzenecarboximidamide
• 化学式: C₁₉H₂₄N₄O₄
• 分子量: 372.424
• InChiKey: UVADNHMLTJNGDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4,4'-pentamethylenedioxydibenzamideoxime 在 盐酸 、 4-二甲氨基吡啶 、 carboxyl esterase 、 cytochrome b5 、 NADH cytochrome b5 reductase 、 human amidoxime reducing component 1 、 N,N'-二环己基碳二亚胺 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 乙醚 、 丙酮 为溶剂， 反应 24.5h， 生成 喷他脒
  参考文献：
  名称：

  Synthesis and biological evaluation of l-valine-amidoximeesters as double prodrugs of amidines

  摘要：

  In general, drugs containing amidines suffer from poor oral bioavailability and are often converted into amidoxime prodrugs to overcome low uptake from the gastrointestinal tract. The esterification of amidoximes with amino acids represents a newly developed double prodrug principle creating derivatives of amidines with both improved oral availability and water solubility. N-valoxybenzamidine (1) is a model compound for this principle, which has been transferred to the antiprotozoic drug pentamidine (8). Prodrug activation depends on esterases and mARC and is thus independent from activation by P450 enzymes. Therefore, drug-drug interactions or side effects will be minimized. The synthesis of these two compounds was established, and their biotransformation was studied in vitro and in vivo. Bioactivation of N-valoxybenzamidine (1) and N,N'-bis(valoxy)pentamidine (7) via hydrolysis and reduction has been demonstrated in vitro with porcine and human subcellular enzyme preparations and the mitochondrial Amidoxime Reducing Component (mARC). Moreover, activation of N-valoxybenzamidine (1) by porcine hepatocytes was studied. In vivo, the bioavailability in rats after oral application of N-valoxybenzamidine (1) was about 88%. Similarly, N,N'-bis(valoxy)pentamidine (7) showed oral bioavailability. Analysis of tissue samples revealed high concentrations of pentamidine (8) in liver and kidney. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.066
• 作为产物：
  描述：

  1,5-二(4-氰基苯氧基)戊烷 在 羟胺 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以94%的产率得到4,4'-pentamethylenedioxydibenzamideoxime
  参考文献：
  名称：

  Clement; Raether, Arzneimittel-Forschung/Drug Research, 1985, vol. 35, # 7, p. 1009 - 1014

  摘要：

  DOI：

文献信息

• SUBSTITUTED TETRAHYDROPYRROLOQUINOLINES
  申请人：Enderle Holger

  公开号：US20100120818A1

  公开（公告）日：2010-05-13

  Compounds of the formula (I), in which R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 and m have the meanings indicated in Claim 1 , can be employed, inter alia, for the treatment of tumours.

  化合物的公式（I），其中R1、R2、R3、R4、R5和R6以及m具有权利要求1中指示的含义，可以用于治疗肿瘤。
• SUBSTITUTED TETRAHYDROQUINOLINES
  申请人：Schiemann Kai

  公开号：US20100022579A1

  公开（公告）日：2010-01-28

  Compounds of the formula (I), in which R 1 , R 2 , R 3 , R 4 , R 5 , X, Y, W, Q 1 , Q 2 , Z, s and m have the meanings indicated in claim 1, can be employed, inter alia, for the treatment of tumours.

  化合物的结构式（I）中，其中R1、R2、R3、R4、R5、X、Y、W、Q1、Q2、Z、s和m具有权利要求书中指定的含义，可用于治疗肿瘤。
• TETRAHYDROBENZOISOXAZOLE AND TETRAHYDROINDAZOLE DERIVATIVES AS MODULATORS OF THE MITOTIC MOTOR PROTEIN
  申请人：Schiemann Kai

  公开号：US20100022530A1

  公开（公告）日：2010-01-28

  Compounds of the formula (I) in which A 1 , A 2 , R 1 , X 1 , X 2 , X 3 , Y, R 2 , Cy and n have meanings indicated in claim 1 , can be employed, inter alia, for the treatment of tumours.

  公式（I）中A1，A2，R1，X1，X2，X3，Y，R2，Cy和n具有权利要求1中所示的含义的化合物，可以用于治疗肿瘤等疾病。
• TETRAHYDROQUINOLINE DERIVATIVES AND THE USE THEREOF FOR THE TREATMENT OF CANCER
  申请人：Schiemann Kai

  公开号：US20100076012A1

  公开（公告）日：2010-03-25

  Compounds of the formula (I), in which E, R 3 , R 4 , R 5 , X, Y, W, Q 1 , Q 2 , Z, s and m have the meanings indicated in claim 1 , can be employed, inter alia, for the treatment of tumours.

  公式（I）的化合物，其中E，R3，R4，R5，X，Y，W，Q1，Q2，Z，s和m具有声明1中指示的含义，可用于治疗肿瘤等疾病。
• Dihydrobenzothiophenes
  申请人：Finsinger Dirk

  公开号：US20070219246A1

  公开（公告）日：2007-09-20

  Compounds of the formula (I) in which W, R 1 , R 2 , R 3 , R 4 , and q have the meanings indicated in Claim 1 , can be employed, inter alia, for the treatment of tumours.

  式(I)中W、R1、R2、R3、R4和q的含义如权利要求书1所示的化合物，可以用于治疗肿瘤等疾病。