N(1)-(3-(ethylamino)propyl)butane-1,4-diamine trihydrochloride | 150417-92-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N(1)-(3-(ethylamino)propyl)butane-1,4-diamine trihydrochloride
• 英文别名: EtSPD trihydrochloride；N'-[3-(ethylamino)propyl]butane-1,4-diamine;hydrochloride
• CAS: 150417-92-8
• 化学式: C₉H₂₃N₃*3ClH
• 分子量: 282.685
• InChiKey: KNTJAAHCDKYDDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.74
• 重原子数：
  13
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  50.1
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N(1)-(3-(ethylamino)propyl)butane-1,4-diamine trihydrochloride 在 recombinant human polyamine oxidase 作用下， 生成 亚精胺 、 N-乙基-1,3-丙二胺 、 四亚甲基二胺
  参考文献：
  名称：

  Metabolism of N-alkylated spermine analogues by polyamine and spermine oxidases

  摘要：

  N-alkylated polyamine analogues have potential as anticancer and antiparasitic drugs. However, their metabolism in the host has remained incompletely defined thus potentially limiting their utility. Here, we have studied the degradation of three different spermine analogues N,N'-bis-(3-ethylaminopropyl)butane-1,4-diamine (DESPM), N-(3-benzyl-aminopropyl)-N'-(3-ethylaminopropyl)butane-1,4-diamine (BnEtSPM) and N,N'-bis-(3-benzylaminopropyl)butane-1,4-diamine (DBSPM) and related mono-alkylated derivatives as substrates of recombinant human polyamine oxidase (APAO) and spermine oxidase (SMO). APAO and SMO metabolized DESPM to EtSPD [K (m(APAO)) = 10 mu M, k (cat(APAO)) = 1.1 s(-1) and K (m(SMO)) = 28 mu M, k (cat(SMO)) = 0.8 s(-1), respectively], metabolized BnEtSPM to EtSPD [K (m(APAO)) = 0.9 mu M, k (cat(APAO)) = 1.1 s(-1) and K (m(SMO)) = 51 mu M, k (cat(SMO)) = 0.4 s(-1), respectively], and metabolized DBSPM to BnSPD [K (m(APAO)) = 5.4 mu M, k (cat(APAO)) = 2.0 s(-1) and K (m(SMO)) = 33 mu M, k (cat(SMO)) = 0.3 s(-1), respectively]. Interestingly, mono-alkylated spermine derivatives were metabolized by APAO and SMO to SPD [EtSPM K (m(APAO)) = 16 mu M, k (cat(APAO)) = 1.5 s(-1); K (m(SMO)) = 25 mu M, k (cat(SMO)) = 8.2 s(-1); BnSPM K (m(APAO)) = 6.0 mu M, k (cat(APAO)) = 2.8 s(-1); K (m(SMO)) = 19 mu M, k (cat(SMO)) = 0.8 s(-1), respectively]. Surprisingly, EtSPD [K (m(APAO)) = 37 mu M, k (cat(APAO)) = 0.1 s(-1); K (m(SMO)) = 48 mu M, k (cat(SMO)) = 0.05 s(-1)] and BnSPD [K (m(APAO)) = 2.5 mu M, k (cat(APAO)) = 3.5 s(-1); K (m(SMO)) = 60 mu M, k (cat(SMO)) = 0.54 s(-1)] were metabolized to SPD by both the oxidases. Furthermore, we studied the degradation of DESPM, BnEtSPM or DBSPM in the DU145 prostate carcinoma cell line. The same major metabolites EtSPD and/or BnSPD were detected both in the culture medium and intracellularly after 48 h of culture. Moreover, EtSPM and BnSPM were detected from cell samples. Present data shows that inducible SMO parallel with APAO could play an important role in polyamine based drug action, i.e. degradation of parent drug and its metabolites, having significant impact on efficiency of these drugs, and hence for the development of novel N-alkylated polyamine analogues.

  DOI：

  10.1007/s00726-009-0429-2
• 作为产物：
  描述：

  在 一水合肼 、 盐酸 作用下， 以 乙醇 、 1,4-二氧六环 、 水 为溶剂， 反应 3.0h， 以376 mg的产率得到N(1)-(3-(ethylamino)propyl)butane-1,4-diamine trihydrochloride
  参考文献：
  名称：

  新型氘标记的N-烷基化多胺衍生物的合成

  摘要：

  合成了单-N-烷基化的二氨基丙烷，亚精胺，亚精胺，对称的双-N-烷基化的亚精胺和不对称的双-N-烷基化的亚精胺的新的二，四和八氘代衍生物。通过在碱性条件下用D 2 O–EtOD混合物交换邻近腈基的质子或/和通过使用LiAlD将腈基还原为CD 2 –NH 2片段，将氘标记物引入RHNCH 2 CH 2 CN中间体中。4。

  DOI：

  10.1016/j.tet.2008.10.071

文献信息

• US4918107A
  申请人：——

  公开号：US4918107A

  公开（公告）日：1990-04-17
• Synthesis of novel deuterium labelled derivatives of N-alkylated polyamines
  作者：Merja R. Häkkinen、Tuomo A. Keinänen、Alex R. Khomutov、Seppo Auriola、Janne Weisell、Leena Alhonen、Juhani Jänne、Jouko Vepsäläinen

  DOI：10.1016/j.tet.2008.10.071

  日期：2009.1

  bis-N-alkylated spermines and unsymmetrically bis-N-alkylated spermines were synthesized. Deuterium labels were introduced into the RHNCH2CH2CN intermediate either by exchanging the protons next to the nitrile group under basic conditions with D2O–EtOD mixture or/and by reducing the nitrile group to a CD2–NH2 fragment with LiAlD4.

  合成了单-N-烷基化的二氨基丙烷，亚精胺，亚精胺，对称的双-N-烷基化的亚精胺和不对称的双-N-烷基化的亚精胺的新的二，四和八氘代衍生物。通过在碱性条件下用D 2 O–EtOD混合物交换邻近腈基的质子或/和通过使用LiAlD将腈基还原为CD 2 –NH 2片段，将氘标记物引入RHNCH 2 CH 2 CN中间体中。4。
• Metabolism of N-alkylated spermine analogues by polyamine and spermine oxidases
  作者：Merja R. Häkkinen、Mervi T. Hyvönen、Seppo Auriola、Robert A. Casero、Jouko Vepsäläinen、Alex R. Khomutov、Leena Alhonen、Tuomo A. Keinänen

  DOI：10.1007/s00726-009-0429-2

  日期：2010.2

  N-alkylated polyamine analogues have potential as anticancer and antiparasitic drugs. However, their metabolism in the host has remained incompletely defined thus potentially limiting their utility. Here, we have studied the degradation of three different spermine analogues N,N'-bis-(3-ethylaminopropyl)butane-1,4-diamine (DESPM), N-(3-benzyl-aminopropyl)-N'-(3-ethylaminopropyl)butane-1,4-diamine (BnEtSPM) and N,N'-bis-(3-benzylaminopropyl)butane-1,4-diamine (DBSPM) and related mono-alkylated derivatives as substrates of recombinant human polyamine oxidase (APAO) and spermine oxidase (SMO). APAO and SMO metabolized DESPM to EtSPD [K (m(APAO)) = 10 mu M, k (cat(APAO)) = 1.1 s(-1) and K (m(SMO)) = 28 mu M, k (cat(SMO)) = 0.8 s(-1), respectively], metabolized BnEtSPM to EtSPD [K (m(APAO)) = 0.9 mu M, k (cat(APAO)) = 1.1 s(-1) and K (m(SMO)) = 51 mu M, k (cat(SMO)) = 0.4 s(-1), respectively], and metabolized DBSPM to BnSPD [K (m(APAO)) = 5.4 mu M, k (cat(APAO)) = 2.0 s(-1) and K (m(SMO)) = 33 mu M, k (cat(SMO)) = 0.3 s(-1), respectively]. Interestingly, mono-alkylated spermine derivatives were metabolized by APAO and SMO to SPD [EtSPM K (m(APAO)) = 16 mu M, k (cat(APAO)) = 1.5 s(-1); K (m(SMO)) = 25 mu M, k (cat(SMO)) = 8.2 s(-1); BnSPM K (m(APAO)) = 6.0 mu M, k (cat(APAO)) = 2.8 s(-1); K (m(SMO)) = 19 mu M, k (cat(SMO)) = 0.8 s(-1), respectively]. Surprisingly, EtSPD [K (m(APAO)) = 37 mu M, k (cat(APAO)) = 0.1 s(-1); K (m(SMO)) = 48 mu M, k (cat(SMO)) = 0.05 s(-1)] and BnSPD [K (m(APAO)) = 2.5 mu M, k (cat(APAO)) = 3.5 s(-1); K (m(SMO)) = 60 mu M, k (cat(SMO)) = 0.54 s(-1)] were metabolized to SPD by both the oxidases. Furthermore, we studied the degradation of DESPM, BnEtSPM or DBSPM in the DU145 prostate carcinoma cell line. The same major metabolites EtSPD and/or BnSPD were detected both in the culture medium and intracellularly after 48 h of culture. Moreover, EtSPM and BnSPM were detected from cell samples. Present data shows that inducible SMO parallel with APAO could play an important role in polyamine based drug action, i.e. degradation of parent drug and its metabolites, having significant impact on efficiency of these drugs, and hence for the development of novel N-alkylated polyamine analogues.