2,5-di(4-aminobutyl)thiophene | 207908-96-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2,5-di(4-aminobutyl)thiophene
• 英文别名: 4-[5-(4-aminobutyl)thien-2-yl]butylamine；2,5-Di(4-aminobutyl)-thiophene；4-[5-(4-aminobutyl)thiophen-2-yl]butan-1-amine
• CAS: 207908-96-1
• 化学式: C₁₂H₂₂N₂S
• 分子量: 226.386
• InChiKey: IGJBDWWXPLFLKK-UHFFFAOYSA-N

物化性质

• 沸点：
  369.9±42.0 °C(Predicted)
• 密度：
  1.038±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,5-di(4-aminobutyl)thiophene 在 sodium hydroxide 、 2-氯-1-甲基吡啶碘化物 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  New polyamine-sensitive inhibitors of the NMDA receptor: Syntheses and pharmacological evaluation

  摘要：

  Derivatives of 5-(4-an-nobutyl)-2-thiophene-octylamine, a potent polyamine-sensitive inhibitor of the NMDA receptor, were synthesized and evaluated as inhibitors of [H-3]MK-801 binding to rat brain membranes. Alkylations of the terminal amino groups reduced inhibitory potency; only incorporation of the amino group of the short 4-aminobutyl arm into a piperidine ring was tolerated. Substitution of the thiophene nucleus with methyl or ethyl, and its replacement by a benzene nucleus, was of minor influence. The corresponding diguanidines exhibited high potency independent of chain length, whereas their sensitivity to spermine was sharply dependent on chain length. Insertion of an amide bond into the long octylamine arm increased sensitivity to spermine and to Tris buffer. Our results indicate that spermine sensitivity of [H-3]MK-801 binding inhibition is responsive to subtle changes in inhibitor structure and represents a promising target for pharmaceutical research. (c) 2006 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.09.017
• 作为产物：
  描述：

  5-(2-噻吩基)戊酸 在 吡啶 、 氢氧化钾 、 三氯化铝 、 氯化亚砜 、 草酰氯 、 氨 、 溴 、 一水合肼 作用下， 以 二硫化碳 、 乙二醇 为溶剂， 反应 0.5h， 生成 2,5-di(4-aminobutyl)thiophene
  参考文献：
  名称：

  Inverse agonists at the polyamine-sensitive modulatory site of the NMDA receptor: 50-fold increase in potency by insertion of an aromatic ring into an alkanediamine chain

  摘要：

  Polyamines like spermine and spermidine increase the opening frequency of the NMDA receptor associated ion channel and, as a consequence, specific binding of non-saturating concentrations of the channel radioligand [H-3]MK-801. Compounds exhibiting the contrary effect have been described as polyamine inverse agonists, with 1,12-dodecanediamine (N-12-N) being one of the most specific ones (IC50 16.5 mu M). Here we describe the synthesis of a series of long-chain alkanediamines, with a thiophene nucleus inserted at various positions, and report the discovery of 5-(4-aminobutyl)-2-thiopheneoctanamine (N-4-T-8-N), which inhibited specific binding of [H-3]MK-801 by 50 % at 0.33 mu M. In the presence of 100 mu M of spermine, 4.0 mu M N-4-T-8-N was necessary to achieve the same degree of inhibition. N-4-T-8-N is the most potent polyamine inverse agonist presently known and should be a useful tool to elucidate the physiological significance of the polyamine regulatory site of the NMDA receptor complex. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(99)80070-1

文献信息

• Oligothiophene compounds inhibit the membrane fusion between H5N1 avian influenza virus and the endosome of host cell
  作者：Zhibo Zhu、Zhili Yao、Xiantian Shen、Zhipeng Chen、Xiangtao Liu、Jon R. Parquette、Shuwen Liu

  DOI：10.1016/j.ejmech.2017.02.040

  日期：2017.4

  Hemagglutinin (HA) which is essential for influenza viral infection and replication has become a target for the design of anti-influenza drugs. A novel series of oligothiophene compounds focused on the target were synthesized as specific inhibitors against the H5 subtype of influenza A viruses because oligothiophene has Pi-Pi stronger pep interactions with residues F110(2) and M24(1) of HA2 side chains. Oligothiophene compounds were designed and synthesized by a series of alkylation, azidation, amination and amidation reactions. The entry inhibitory activities of those compounds were tested at a cellular level against H5N1 influenza pseudovirus. Compound 3sf was revealed as the most active inhibitor in this series with an IC50 of 0.029 mM. The activity of 3sf is almost 1000 times that of the positive reference compound (CL-385319). A structure-activity analysis of these compounds demonstrated that the size of the oligothiophene compounds was very important for the inhibitory activity. Four compounds (3sk, 3sf, 3sc and 4sc) of strong inhibitiory activity against H5N1 influenza pseudovirus were assessed against H1N1 influenza virus MDCK. They also showed strong inhibitiory activity with IC50s of 3.292 mu M, 1.240 mu M, 1.119 mu M and 0.768 mu M, respectively. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Efficient Intermolecular Charge Transport in Self-Assembled Fibers of Mono- and Bithiophene Bisurea Compounds
  作者：Franck S. Schoonbeek、Jan H. van Esch、Bas Wegewijs、Diederik B. A. Rep、Matthijs P. de Haas、Teun M. Klapwijk、Richard M. Kellogg、Ben L. Feringa

  DOI：10.1002/(sici)1521-3773(19990517)38:10<1393::aid-anie1393>3.0.co;2-h

  日期：1999.5.17

  Hydrogen bonds between urea units allow self-organization of π systems in mono- and bithiophenes into fibers as shown schematically. In these fibers there is a surprisingly high mobility of charge carriers as determined by pulse-radiolysis time-resolved microwave conductivity measurements.
• New polyamine-sensitive inhibitors of the NMDA receptor: Syntheses and pharmacological evaluation
  作者：Thomas Pöhler、Oliver Schadt、Daniela Niepel、Patrick Rebernik、Michael L. Berger、Christian R. Noe

  DOI：10.1016/j.ejmech.2006.09.017

  日期：2007.2

  Derivatives of 5-(4-an-nobutyl)-2-thiophene-octylamine, a potent polyamine-sensitive inhibitor of the NMDA receptor, were synthesized and evaluated as inhibitors of [H-3]MK-801 binding to rat brain membranes. Alkylations of the terminal amino groups reduced inhibitory potency; only incorporation of the amino group of the short 4-aminobutyl arm into a piperidine ring was tolerated. Substitution of the thiophene nucleus with methyl or ethyl, and its replacement by a benzene nucleus, was of minor influence. The corresponding diguanidines exhibited high potency independent of chain length, whereas their sensitivity to spermine was sharply dependent on chain length. Insertion of an amide bond into the long octylamine arm increased sensitivity to spermine and to Tris buffer. Our results indicate that spermine sensitivity of [H-3]MK-801 binding inhibition is responsive to subtle changes in inhibitor structure and represents a promising target for pharmaceutical research. (c) 2006 Elsevier Masson SAS. All rights reserved.
• Inverse agonists at the polyamine-sensitive modulatory site of the NMDA receptor: 50-fold increase in potency by insertion of an aromatic ring into an alkanediamine chain
  作者：Michael L. Berger、Clemens Schödl、Christian R. Noe

  DOI：10.1016/s0223-5234(99)80070-1

  日期：1998.1

  Polyamines like spermine and spermidine increase the opening frequency of the NMDA receptor associated ion channel and, as a consequence, specific binding of non-saturating concentrations of the channel radioligand [H-3]MK-801. Compounds exhibiting the contrary effect have been described as polyamine inverse agonists, with 1,12-dodecanediamine (N-12-N) being one of the most specific ones (IC50 16.5 mu M). Here we describe the synthesis of a series of long-chain alkanediamines, with a thiophene nucleus inserted at various positions, and report the discovery of 5-(4-aminobutyl)-2-thiopheneoctanamine (N-4-T-8-N), which inhibited specific binding of [H-3]MK-801 by 50 % at 0.33 mu M. In the presence of 100 mu M of spermine, 4.0 mu M N-4-T-8-N was necessary to achieve the same degree of inhibition. N-4-T-8-N is the most potent polyamine inverse agonist presently known and should be a useful tool to elucidate the physiological significance of the polyamine regulatory site of the NMDA receptor complex. (C) Elsevier, Paris.