N-[2-(1H-indol-3-yl)ethyl]-N′,N′-dimethylpropane-1,3-diamine | 1226213-83-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-[2-(1H-indol-3-yl)ethyl]-N′,N′-dimethylpropane-1,3-diamine
• 英文别名: N1-(2-(1H-Indol-3-yl)ethyl)-N3,N3-dimethylpropane-1,3-diamine；N-[2-(1H-indol-3-yl)ethyl]-N',N'-dimethylpropane-1,3-diamine
• CAS: 1226213-83-7
• 化学式: C₁₅H₂₃N₃
• 分子量: 245.368
• InChiKey: WXDCWQNNGHIWNR-UHFFFAOYSA-N

物化性质

• 沸点：
  407.9±30.0 °C(Predicted)
• 密度：
  1.051±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  31.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-(2-溴乙基)吲哚 、 N,N-二甲基-1,3-二氨基丙烷 以 乙醇 为溶剂， 反应 5.0h， 以80%的产率得到N-[2-(1H-indol-3-yl)ethyl]-N′,N′-dimethylpropane-1,3-diamine
  参考文献：
  名称：

  Noncompetitive Inhibition of Indolethylamine-N-methyltransferase by N,N-Dimethyltryptamine and N,N-Dimethylaminopropyltryptamine

  摘要：

  Indolethylamine-N-methyltransferase (INMT) is a Class 1 transmethylation enzyme known for its production of N,N-dimethyltryptamine (DMT), a hallucinogen with affinity for various serotonergic, adrenergic, histaminergic, dopaminergic, and sigma-1 receptors. DMT is produced via the action of INMT on the endogenous substrates tryptamine and S-adenosyl-L-methionine (SAM). The biological, biochemical, and selective small molecule regulation of INMT enzyme activity remain largely unknown. Kinetic mechanisms for inhibition of rabbit lung INMT (rabINMT) by the product, DMT, and by a new novel tryptamine derivative were determined. After Michaelis-Menten and Lineweaver-Burk analyses had been applied to study inhibition, DMT was found to be a mixed competitive and noncompetitive inhibitor when measured against tryptamine. The novel tryptamine derivative, N[2-(1H-indol-3-yl)ethyl]-N',Ni-dimethylpropane-1,3-diamine (propyl dimethyl amino tryptamine or PDAT), was shown to inhibit rabINMT by a pure noncompetitive mechanism when measured against tryptamine with a K-i, of 84 mu M. No inhibition by PDAT was observed at 2 mM when it was tested against structurally similar Class 1 methyltransferases, such as human phenylethanolamine-N-methyltransferase (hPNMT) and human nicotinamide-N-methyltransferase (hNNMT), indicating selectivity for INMT. The demonstration of noncompetitive mechanisms for INMT inhibition implies the presence of an inhibitory allosteric site. In silico analyses using the computer modeling software Autodock and the rabINMT sequence threaded onto the human INMT (hINMT) structure (Protein Data Bank entry 2A14) identified an N-terminal helix-loop-helix non-active site binding region of the enzyme. The energies for binding of DMT and PDAT to this region of rabINMT, as determined by Autodock, were -6.34 and -7.58 kcal/mol, respectively. Assessment of the allosteric control of INMT may illuminate new biochemical pathway(s) underlying the biology of INMT.

  DOI：

  10.1021/bi500175p

文献信息

• Noncompetitive Inhibition of Indolethylamine-<i>N</i>-methyltransferase by <i>N</i>,<i>N</i>-Dimethyltryptamine and <i>N</i>,<i>N</i>-Dimethylaminopropyltryptamine
  作者：Uyen B. Chu、Sevahn K. Vorperian、Kenneth Satyshur、Kelsey Eickstaedt、Nicholas V. Cozzi、Timur Mavlyutov、Abdol R. Hajipour、Arnold E. Ruoho

  DOI：10.1021/bi500175p

  日期：2014.5.13

  Indolethylamine-N-methyltransferase (INMT) is a Class 1 transmethylation enzyme known for its production of N,N-dimethyltryptamine (DMT), a hallucinogen with affinity for various serotonergic, adrenergic, histaminergic, dopaminergic, and sigma-1 receptors. DMT is produced via the action of INMT on the endogenous substrates tryptamine and S-adenosyl-L-methionine (SAM). The biological, biochemical, and selective small molecule regulation of INMT enzyme activity remain largely unknown. Kinetic mechanisms for inhibition of rabbit lung INMT (rabINMT) by the product, DMT, and by a new novel tryptamine derivative were determined. After Michaelis-Menten and Lineweaver-Burk analyses had been applied to study inhibition, DMT was found to be a mixed competitive and noncompetitive inhibitor when measured against tryptamine. The novel tryptamine derivative, N[2-(1H-indol-3-yl)ethyl]-N',Ni-dimethylpropane-1,3-diamine (propyl dimethyl amino tryptamine or PDAT), was shown to inhibit rabINMT by a pure noncompetitive mechanism when measured against tryptamine with a K-i, of 84 mu M. No inhibition by PDAT was observed at 2 mM when it was tested against structurally similar Class 1 methyltransferases, such as human phenylethanolamine-N-methyltransferase (hPNMT) and human nicotinamide-N-methyltransferase (hNNMT), indicating selectivity for INMT. The demonstration of noncompetitive mechanisms for INMT inhibition implies the presence of an inhibitory allosteric site. In silico analyses using the computer modeling software Autodock and the rabINMT sequence threaded onto the human INMT (hINMT) structure (Protein Data Bank entry 2A14) identified an N-terminal helix-loop-helix non-active site binding region of the enzyme. The energies for binding of DMT and PDAT to this region of rabINMT, as determined by Autodock, were -6.34 and -7.58 kcal/mol, respectively. Assessment of the allosteric control of INMT may illuminate new biochemical pathway(s) underlying the biology of INMT.