(E)-2-butene-1,4-diyl-bis(mesitylenesulfonate) | 206991-70-0

• 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: (E)-2-butene-1,4-diyl-bis(mesitylenesulfonate)
• 英文别名: (E)-2-butene-1,4-diyl bis[mesitylenesulfonate]；[(E)-4-(2,4,6-trimethylphenyl)sulfonyloxybut-2-enyl] 2,4,6-trimethylbenzenesulfonate
• CAS: 206991-70-0
• 化学式: C₂₂H₂₈O₆S₂
• 分子量: 452.593
• InChiKey: BXNPNIHSCGFACU-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N'-bis(mesitylenesulfonyl)-N-ethyl-1,3-diaminopropane 、 (E)-2-butene-1,4-diyl-bis(mesitylenesulfonate) 在 sodium hydride 作用下， 生成 (E)-3,7,12,16-tetrakis(mesitylenesulfonyl)-3,7,12,16-tetraazaoctadec-9-ene
  参考文献：
  名称：

  Conformationally Restricted Analogues of ¹N,¹²N-Bisethylspermine:  Synthesis and Growth Inhibitory Effects on Human Tumor Cell Lines

  摘要：

  Eight analogues of N-1,N-12-bisethylspermine (BES) with restricted conformations were synthesized in the search for new spermine mimetics with cytotoxic activities. By replacing the central butane segment of BES with a 1,2-disubstituted cyclopropane ring, a pair of cis/trans-isomers was obtained that introduced a spatial constraint in the otherwise freely mobile butane chain. An analogous pair of isomers was obtained when the butane segment was replaced with a 1,2-disubstituted cyclobutane ring or with a 2-butene residue. The six new BES analogues thus obtained.(three pairs of cis/trans-isomers) were growth inhibitory at low-micromolar concentrations against four human tumor cell lines (A549, HT-29, U251MG, and DU145) but were less growth inhibitory against two other human tumor cell lines (PC-3 and MCF7). N-1,N-12-Bisethylspermyne, where the central butane segment of BES was replaced by the rigid 2-butyne segment, was devoid of growth inhibitory activity against five of the six human cell lines studied (DU145 being the only exception), a clear indication of the importance of conformational mobility at the N-4,N-9-butane segment of BES for its biological activity. When the butane segment was replaced by a benzene-1,2-dimethyl residue, the resulting BES analogue was devoid of growth inhibitory activity despite its cisoid conformation. The cytotoxicity of the analogues does not seem to be directly related to their uptake by the cells or to their effects on cellular polyamine levels. BES analogues with restricted conformations but which contained the equivalent of a two-carbon unit, rather than the natural four-carbon unit, at the central segment, such as 1,2-diaminocyclopropyl or 1,2-diaminocyclobutyl derivatives, were devoid of growth inhibitory effects at the concentrations studied. The development of conformationally restricted polyamine analogues appears to show promise in the further quest for polyamine-related therapeutic agents with specificity of action.

  DOI：

  10.1021/jm980172v
• 作为产物：
  描述：

  2,4,6-三甲基苯磺酰氯 、 反-2-丁烯-1,4-二醇 在 氢氧化钾 、 苄基三乙基溴化铵 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以77%的产率得到(E)-2-butene-1,4-diyl-bis(mesitylenesulfonate)
  参考文献：
  名称：

  Conformationally Restricted Analogues of ¹N,¹²N-Bisethylspermine:  Synthesis and Growth Inhibitory Effects on Human Tumor Cell Lines

  摘要：

  Eight analogues of N-1,N-12-bisethylspermine (BES) with restricted conformations were synthesized in the search for new spermine mimetics with cytotoxic activities. By replacing the central butane segment of BES with a 1,2-disubstituted cyclopropane ring, a pair of cis/trans-isomers was obtained that introduced a spatial constraint in the otherwise freely mobile butane chain. An analogous pair of isomers was obtained when the butane segment was replaced with a 1,2-disubstituted cyclobutane ring or with a 2-butene residue. The six new BES analogues thus obtained.(three pairs of cis/trans-isomers) were growth inhibitory at low-micromolar concentrations against four human tumor cell lines (A549, HT-29, U251MG, and DU145) but were less growth inhibitory against two other human tumor cell lines (PC-3 and MCF7). N-1,N-12-Bisethylspermyne, where the central butane segment of BES was replaced by the rigid 2-butyne segment, was devoid of growth inhibitory activity against five of the six human cell lines studied (DU145 being the only exception), a clear indication of the importance of conformational mobility at the N-4,N-9-butane segment of BES for its biological activity. When the butane segment was replaced by a benzene-1,2-dimethyl residue, the resulting BES analogue was devoid of growth inhibitory activity despite its cisoid conformation. The cytotoxicity of the analogues does not seem to be directly related to their uptake by the cells or to their effects on cellular polyamine levels. BES analogues with restricted conformations but which contained the equivalent of a two-carbon unit, rather than the natural four-carbon unit, at the central segment, such as 1,2-diaminocyclopropyl or 1,2-diaminocyclobutyl derivatives, were devoid of growth inhibitory effects at the concentrations studied. The development of conformationally restricted polyamine analogues appears to show promise in the further quest for polyamine-related therapeutic agents with specificity of action.

  DOI：

  10.1021/jm980172v

文献信息

• Oligoamine compounds and derivatives thereof for cancer therapy
  申请人：SLIL Biomedical Corporation

  公开号：US20030130356A1

  公开（公告）日：2003-07-10

  Oligoamine compounds with anti-cancer and anti-proliferative activity are provided, as well as methods for making and using the compounds. The compounds are shown to be active against prostate cancer cell lines and against prostate cancer tumors in mice. The compounds are also useful in treatment of breast cancer and other cancers.

  提供具有抗癌和抗增殖活性的寡胺化合物，以及制备和使用这些化合物的方法。这些化合物已被证明对前列腺癌细胞系和小鼠前列腺癌肿瘤具有活性。这些化合物还在乳腺癌和其他癌症的治疗中具有用途。
• [EN] CONFORMATIONALLY RESTRICTED POLYAMINES AND THEIR USE AS ANTINEOPLASTIC AGENTS<br/>[FR] POLYAMINES DE CONFORMATION RESTREINTE ET LEUR UTILISATION EN TANT QU'AGENTS ANTINEOPLASIQUES
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：WO1998017624A1

  公开（公告）日：1998-04-30

  (EN) Compounds of the Formula (I): E-NH-D-NH-B-A-B-NH-D-NH-E, wherein A is C2-C6 alkene, C3-C6 cycloalkyl, cycloalkenyl, or cycloaryl; B is independently a single bond, C1-C6 alkyl alkenyl; D is independently C1-C6 alkyl or alkenyl, or C3-C6 cycloalkyl, cycloalkenyl, or cycloaryl; and E is independently H, C1-C6 alkyl or alkenyl; and pharmaceutically suitable salts thereof; a synthetic method therefor, pharmaceutical dosage forms containing one of more of these compounds, and use of these compounds in the treatment of neoplastic cell growth, are disclosed.(FR) Composés représentés par la formule (I): E-NH-D-NH-B-A-B-NH-D-NH-E dans laquelle A représente alkène C2-C6, cycloalkyle C3-C6, cycloalkényle ou cycloaryle; B représente indépendamment une liaison simple, alkylalkényle C1-C6; D représente indépendamment alkyle C1-C6 ou alkényle ou cycloalkyle C3-C6, cycloalkényle ou cycloaryle; E représente indépendamment H, alkyle C1-C6 ou alkényle; leurs sels acceptables sur le plan pharmaceutique; leur procédé de synthèse, formes galéniques pharmaceutiques contenant un ou plusieurs de ces composés et utilisation de ces composés pour la traitement de la prolifération cellulaire néoplasique.

  化合物的公式(I)为：E-NH-D-NH-B-A-B-NH-D-NH-E，其中A为C2-C6烯烃，C3-C6环烷基，环烯基或环芳基；B独立地为单键，C1-C6烷基烯基；D独立地为C1-C6烷基或烯基，或C3-C6环烷基，环烯基或环芳基；E独立地为H，C1-C6烷基或烯基；以及其在药学上适用的盐；公开了一种合成方法，含有其中一个或多个化合物的药物剂量形式，以及使用这些化合物治疗肿瘤细胞生长的方法。
• OLIGOAMINE COMPOUNDS AND DERIVATIVES THEREOF FOR CANCER THERAPY
  申请人：Frydman Benjamin

  公开号：US20090124832A1

  公开（公告）日：2009-05-14

  Oligoamine compounds with anti-cancer and anti-proliferative activity are provided, as well as methods for making and using the compounds. The compounds are shown to be active against prostate cancer cell lines and against prostate cancer tumors in mice. The compounds are also useful in treatment of breast cancer and other cancers.

  提供具有抗癌和抗增殖活性的寡胺化合物，以及制备和使用这些化合物的方法。这些化合物已被证明对前列腺癌细胞系和小鼠前列腺癌肿瘤具有活性。这些化合物还可用于治疗乳腺癌和其他癌症。
• Novel Synthetic Polyamines Are Effective in the Treatment of Experimental Microsporidiosis, an Opportunistic AIDS-Associated Infection
  作者：Cyrus J. Bacchi、Louis M. Weiss、Schenella Lane、Benjamin Frydman、Aldonia Valasinas、Venodhar Reddy、Jerry S. Sun、Laurence J. Marton、Imitiaz A. Khan、Magali Moretto、Nigel Yarlett、Murray Wittner

  DOI：10.1128/aac.46.1.55-61.2002

  日期：2002.1

  Microsporidia are eukaryotic obligate intracellular protists that are emerging pathogens in immunocompromised hosts, such as patients with AIDS or patients who have undergone organ transplantation. We have demonstrated in vitro and in vivo that synthetic polyamine analogs are effective antimicrosporidial agents with a broad therapeutic window. CD8-knockout mice or nude mice infected with the microsporidianEncephalitozoon cuniculiwere cured when they were treated with four different novel polyamine analogs at doses ranging from 1.25 to 5 mg/kg of body weight/day for a total of 10 days. Cured animals demonstrated no evidence of parasitemia by either PCR or histologic staining of tissues 30 days after untreated control animals died.

  摘要微孢子虫是真核细胞内强制性原生生物，是免疫功能低下宿主（如艾滋病患者或接受过器官移植的患者）中新出现的病原体。我们已在体外和体内证明，合成多胺类似物是有效的抗孢子虫药物，具有广泛的治疗窗口期。用四种不同的新型多胺类似物按每公斤体重 1.25 至 5 毫克/天的剂量治疗小鼠或裸鼠，共 10 天后，感染阴沟脑膜炎小孢子虫的小鼠或裸鼠痊愈。治愈的动物在未经治疗的对照组动物死亡 30 天后，通过 PCR 或组织学染色检查，均未发现寄生虫血症的迹象。
• Polyamines and their use in therapy
  申请人：Cellgate, Inc.

  公开号：EP1698629A2

  公开（公告）日：2006-09-06

  Novel conformationally restricted polyamine analogs are provided, as well as compositions comprising these novel polyamine analogs. Methods of using the novel polyamine analogs in treatment of diseases such as cancer are also provided. Also provided is a method of delivering these analogs specifically to tumor cells by covalently attaching polyamine analogs to porphyrin compounds, along with novel polyamine-porphyrin covalent conjugates.

  本文提供了构象受限的新型多胺类似物以及包含这些新型多胺类似物的组合物。还提供了使用新型多胺类似物治疗癌症等疾病的方法。此外，还提供了一种通过将多胺类似物与卟啉化合物共价连接，以及新型多胺-卟啉共价结合物，将这些类似物特异性地递送至肿瘤细胞的方法。