N-{3-[(4-aminobutyl)amino]propyl}(phenylmethyl)amine

• 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: N-{3-[(4-aminobutyl)amino]propyl}(phenylmethyl)amine
• 英文别名: N1-(3-benzylaminopropyl)butane-1,4-diamine；BnSPD；N'-[3-(benzylamino)propyl]butane-1,4-diamine
• 化学式: C₁₄H₂₅N₃
• 分子量: 235.373
• InChiKey: NAPQCIUQGHGKEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  50.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-{3-[(4-aminobutyl)amino]propyl}(phenylmethyl)amine 在 recombinant human polyamine oxidase 作用下， 生成 亚精胺 、 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：

  DBSPM tetrahydrochloride 在 recombinant human polyamine oxidase 作用下， 生成 N-{3-[(4-aminobutyl)amino]propyl}(phenylmethyl)amine
  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

文献信息

• POLYAMINE TRANSPORT INHIBITORS AS NOVEL THERAPEUTICS
  申请人：Phanstiel Otto

  公开号：US20120172449A1

  公开（公告）日：2012-07-05

  Novel polyamine transport inhibitors have been synthesized and demonstrated to block the uptake of native polyamines into human cancer cells. A combination therapy of the transport inhibitor and DFMO (a drug which blocks polyamine biosynthesis) provided synergistic activity against a metastatic human colon cancer cell line. The strategy uses polyamine depletion and polyamine metabolism to generate reactive oxygen species within cells as a novel way to treat cancers. This approach may be implemented for widespread use in the treatment of diseases which rely upon polyamine transport activity for proliferation.

  新型聚胺运输抑制剂已经合成并证明可以阻止天然聚胺进入人类癌细胞。运输抑制剂和DFMO（一种阻止聚胺生物合成的药物）的联合治疗对转移性人类结肠癌细胞系表现出协同作用。该策略利用聚胺耗竭和聚胺代谢在细胞内产生活性氧自由基的新方法来治疗癌症。这种方法可以在依赖聚胺运输活性进行增殖的疾病的广泛治疗中实施。
• Polyamine for use as a medicine in the treatment of neoplasms
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0162413A2

  公开（公告）日：1985-11-27

  This invention relates to the use of certain polyamines in the treatment of neoplasms or in conjunctive therapy with ornithine decarboxylase inhibitors and/or S-adeno-sylme- thionine decarboxylase inhibitors or in conjunction with other known cytotoxic agents, or with interferon.

  本发明涉及某些多胺在治疗肿瘤或与鸟氨酸脱羧酶抑制剂和/或 S-腺苷-硫氨酸脱羧酶抑制剂或与其他已知的细胞毒剂或干扰素联合治疗中的应用。
• REDUCTION OF HAIR GROWTH
  申请人：THE GILLETTE COMPANY

  公开号：EP1049444A1

  公开（公告）日：2000-11-08
• US9212131B2
  申请人：——

  公开号：US9212131B2

  公开（公告）日：2015-12-15
• US9730902B2
  申请人：——

  公开号：US9730902B2

  公开（公告）日：2017-08-15