N,N'-bis(2,4,6-trimethylbenzenesulfonyl)-1,4-butanediamine | 161452-28-4

• 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,N'-bis(2,4,6-trimethylbenzenesulfonyl)-1,4-butanediamine
• 英文别名: N¹,N⁴-bis(mesitylenesulfonyl)putrescine；N¹,N⁴-dimesitylenesulphonylputrescine；bis-1,4-(2,4,6-trimethylbenzenesulfonamido)butane；N,N'-bis(mesitylenesulfonyl)-1,4-butanediamine；N,N'-bis(mesitylenesulfonyl)-1,4-butadiene；1,4-bis(mesitylenesulfonyl)putrescine；N,N'-bis(mesitylenesulfonyl)putrescine；2,4,6-trimethyl-N-[4-[(2,4,6-trimethylphenyl)sulfonylamino]butyl]benzenesulfonamide
• CAS: 161452-28-4
• 化学式: C₂₂H₃₂N₂O₄S₂
• 分子量: 452.639
• InChiKey: WIFHDXKTGPTOFJ-UHFFFAOYSA-N

物化性质

• 沸点：
  618.2±65.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N'-bis(2,4,6-trimethylbenzenesulfonyl)-1,4-butanediamine 在 sodium hydride 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 23.58h， 生成 N5,N10-bis(mesitylenesulfonyl)homospermine
  参考文献：
  名称：

  Polyamine Analogue Regulation of NMDA MK-801 Binding:  A Structure−Activity Study

  摘要：

  A series of analogues and homologues of spermine were synthesized, and their impact on MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor was evaluated. These tetraamines encompass both linear and cyclic compounds. The linear molecules include norspermine, N-1,N-11-diethylnorspermine, N-1,N-13-bis(2,2,2-trifluoroethyl)spermine, homospermine, and N-1,N-14-diethylhomospermine. The cyclic tetraamines consist of the piperidine analogues N-1-N-3-bis(4-piperidinyl)-1,3-diaminopropane, N-1,N-4-bis(4-piperidinyl)-1,4-diaminobutane, N-1,N-4-bis(4-piperidinylmethyl)-1,4-diaminobutane, and N-1,N-4-bis[2-(4-piperidinyl)ethyl]-1,4-diaminobutane and the pyridine analogues N-1-N-3-bis(4-pyridyl)-1,3-diaminopropane, N-1,N-4-bis(4-pyridyl)-1,4-diaminobutane, N-1,N-4-bis(4-pyridylmethyl)-1,4-diaminobutane, and N-1,N-4-bis[2-(4-pyridyl)-ethyl]-1,4-diaminobutane. This structure-activity set makes it possible to establish the importance of charge, intercharge distance, and terminal nitrogen substitution on polyamine-regulated MK-801 binding in the NMDA channel. Four families of tetraamines are included in this set: norspermines, spermines, homospermines, and tetraazaoctadecanes. Calculations employing a SYBYL modeling program revealed that the distance between terminal nitrogens ranges between 12.62 and 19.61 Angstrom. The tetraamines are constructed such that within families cyclics and acyclics have similar lengths but different nitrogen pK(a)'s and thus different protonation, or charge, states at physiological pH. The pK(a) values-for all nitrogens of each molecule and its protonation state at physiological pH are described. The modifications at the' terminal nitrogens include introduction of ethyl and beta,beta,beta-trifluoroethyl groups and incorporation into piperidinyl or pyridyl systems. The studies clearly indicate that polyamine length, charge, and terminal nitrogen substitution have a significant effect on how the tetraamine regulates MK-801 binding to the NMDA receptor. Thus a structure-activity basis set on which future design of MK-801 agonists and antagonists can be based is now available.

  DOI：

  10.1021/jm960545x
• 作为产物：
  描述：

  2,4,6-三甲基苯磺酰氯 、 四亚甲基二胺 在 盐酸 、 水 、 乙醇 作用下， 以 二氯甲烷 、 sodium hydroxide 为溶剂， 反应 24.0h， 以to give 50.46 g (90%) of (1) as needles的产率得到N,N'-bis(2,4,6-trimethylbenzenesulfonyl)-1,4-butanediamine
  参考文献：
  名称：

  Analogs of biologically active, naturally occurring polyamines, pharmaceutical compositions and methods of treatment

  摘要：

  具有以下公式的多胺物质：或其与药学上可接受的酸的盐，其中：R1-R6可以相同或不同，是烷基，芳基，芳基烷基，环烷基，可以通过至少一个醚氧原子中断的烷基链，或氢; N1、N2、N3和N4是氮原子，在生理pH下能够质子化; a和b可以相同或不同，是1到4的整数; A、B和C可以相同或不同，是桥连基团，有效地保持氮原子之间的距离，使多胺物质：(i)在向人类或非人类动物施用后能够被目标细胞吸收; (ii)在被目标细胞吸收后，通过正电荷氮原子之间的静电相互作用与目标细胞内的细胞内天然多胺物质基本相同地竞争性结合生物学反离子;在细胞中与生物学反离子结合后，多胺物质的生物学功能与细胞内多胺物质不同，多胺物质不是自然发生的;以及包含多胺物质的药物组合物和治疗需要抗肿瘤治疗的患者的方法。

  公开号：

  US07094808B2

文献信息

• Cycloalkyl substituted polyamines for cancer therapy and methods of synthesis therefor
  申请人：SLIL Biomedical Corporation

  公开号：US20030195377A1

  公开（公告）日：2003-10-16

  Conformationally restricted polyamine compounds useful in treatment of cancer and other diseases marked by abnormal cell proliferation are disclosed. Improved methods of synthesizing such compounds are also disclosed. In one method of the invention, a carbene-bearing or carbene equivalent-bearing compound is reacted with the double bond of an alkene compound to form a cyclopropyl ring as the first step in the synthesis.

  抑制构象限制的多胺化合物可用于治疗癌症和其他以异常细胞增殖为特征的疾病。改进的合成这类化合物的方法也被揭示。在该发明的一种方法中，带有卡宾基或卡宾等效基团的化合物与烯烃化合物的双键发生反应，形成环丙基环作为合成的第一步。
• Methods and compositions for the treatment of neurodegeneration
  申请人：University Of Florida Research Foundation, Inc.

  公开号：US05886051A1

  公开（公告）日：1999-03-23

  Methods and pharmaceutical compositions in unit dosage form for treating neurodegeneration in a human or non-human animal afflicted therewith wherein the active agent is a therapeutically effective amount of a polyamine having the formula: ##STR1## or a salt thereof with a pharmaceutically acceptable acid wherein: R.sub.1 and R.sub.6 may be the same or different and are hydrogen, alkyl, hydrocarbyl aryl, hydrocarbyl aryl alkyl, cycloalkyl, or any of the foregoing wherein the alkyl chain is interrupted by at least one etheric oxygen atom; N.sup.1, N.sup.2, N.sup.3 and N.sup.4 are nitrogen atoms capable of protonation at physiological pH's; a and b may be the same or different and are integers from 1 to 4; A, B and C may be the same or different and are bridging groups of variable length.

  用于治疗人类或非人类动物神经退行性疾病的单剂量形式的方法和药物组合物，其中活性药物是具有以下结构的聚胺的治疗有效量或其与药用酸的盐：R.sub.1和R.sub.6可以相同也可以不同，是氢、烷基、烃基芳基、烃基芳基烷基、环烷基或前述任何其中烷基链被至少一个醚氧原子打断的物质；N.sup.1、N.sup.2、N.sup.3和N.sup.4是在生理pH下能够质子化的氮原子；a和b可以相同也可以不同，是从1到4的整数；A、B和C可以相同也可以不同，是可变长度的桥联基。
• Polyamine Analogue Antidiarrheals:  A Structure−Activity Study
  作者：Raymond J. Bergeron、Jan Wiegand、James S. McManis、William R. Weimar、Richard E. Smith、Samuel E. Algee、Tammy L. Fannin、Michael A. Slusher、Patti S. Snyder

  DOI：10.1021/jm000277+

  日期：2001.1.1

  spermine polyamine analogues and their evaluation as antidiarrheals are described. Each compound was assessed in a rodent castor oil-induced diarrhea model for its ability to reduce stool output and weight loss in a dose-dependent manner. The spermine pharmacophore is shown to be an excellent platform from which to construct antidiarrheals. The activity of the compounds is very dependent on both the nature

  描述了一组精胺多胺类似物的合成及其作为止泻药的评价。在啮齿动物蓖麻油诱发的腹泻模型中评估每种化合物降低粪便量和体重减轻的能力，这些剂量呈剂量依赖性。精胺药效基团被证明是构建止泻药的绝佳平台。化合物的活性非常取决于末端烷基的性质和分隔氮的亚甲基间隔基的几何形状。毒性特征还完全取决于这些相同的结构特征。根据皮下剂量反应数据和毒性概况，将两种化合物N（1），N（12）-二异丙精胺和N（1），N（12）-二乙基精胺进行了更全面的评估。这些测量包括正式的急性和慢性毒性试验，药物和代谢组织分布研究，以及这些类似物对组织多胺库的影响的评估。最后，N，N′-双[3-（乙基氨基）丙基]-反式1，4-环己二胺的显着活性强调需要进一步探索该构架作为构建其他止泻药的药效基团。
• [EN] POLYAMINE PRODRUGS AND POLYAMINE PRODRUG FORMULATIONS<br/>[FR] PROMÉDICAMENTS DE POLYAMINE ET FORMULATIONS DE PROMÉDICAMENT DE POLYAMINE
  申请人：UNIV NEBRASKA

  公开号：WO2019173446A1

  公开（公告）日：2019-09-12

  Provided herein are copolymers comprising monomers of a polyamine and a degradable linker, and further comprising a stabilizing moiety, a fluorinated moiety, a poly(ethylene glycol) (PEG) which is optionally substituted with a targeting moiety, or a combination thereof. Also provided are nanoparticles comprising copolymers as described herein, and methods of using the copolymers and nanoparticles for treating diseases or disorders, e.g., Snyder Robinson Disease or cancer.

  本文提供了由聚胺和可降解连接剂单体组成的共聚物，进一步包括稳定基团、氟化基团、聚乙二醇（PEG），可选择用靶向基团替代，或其组合。本文还提供了包括上述共聚物的纳米粒子，并提供了使用这些共聚物和纳米粒子治疗疾病或疾病的方法，例如Snyder Robinson病或癌症。
• Biologically active spermidine analogues, pharmaceutical compositions and methods of treatment
  申请人：——

  公开号：US20020045780A1

  公开（公告）日：2002-04-18

  Polyamines having the formula: 1 or a salt thereof with a pharmaceutically acceptable acid wherein: R 1 -R 5 may be the same or different and are alkyl, aryl, aryl alkyl, cycloalkyl or hydrogen; at least one of R 1 and R 2 and at least one of R 4 and R 5 are not hydrogen, and any of the alkyl chains may optionally be interrupted by at least one etheric oxygen atom, excluding N 1 ,N 3 -diethylspermidine and N 1 ,N 3 -dipropylspermidine; and A and B are bridging groups which effectively maintain the distance between the nitrogen atoms such that the polyamine: (i) is capable of uptake by a target cell upon administration of the polyamine to a human or non-human animal; and (ii) upon uptake by the target cell, competitively binds via an electrostatic interaction between the positively charged nitrogen atoms to substantially the same biological counter-anions as the intracellular natural polyamines in the target cell.

  具有以下公式1或其药学上可接受的酸盐的多胺，其中：R1-R5可以相同或不同，且为烷基，芳基，芳基烷基，环烷基或氢；R1和R2中至少有一个，以及R4和R5中至少有一个不是氢，任何烷基链都可以选择性地被至少一个醚氧原子中断，但不包括N1，N3-二乙基亚精胺和N1，N3-二丙基亚精胺；A和B是桥接基团，有效地保持氮原子之间的距离，使得多胺：（i）在将多胺用于人类或非人类动物的治疗时，能够被目标细胞吸收；（ii）在被目标细胞吸收后，通过正电荷氮原子之间的静电相互作用与目标细胞中的细胞内天然多胺基本相同地竞争性结合生物计数离子。