(Z)-2-butene-1,4-diyl-bis(mesitylenesulfonate) | 206991-71-1

• 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: (Z)-2-butene-1,4-diyl-bis(mesitylenesulfonate)
• 英文别名: (Z)-2-butene-1,4-diyl bis[mesitylenesulfonate]；[(Z)-4-(2,4,6-trimethylphenyl)sulfonyloxybut-2-enyl] 2,4,6-trimethylbenzenesulfonate
• CAS: 206991-71-1
• 化学式: C₂₂H₂₈O₆S₂
• 分子量: 452.593
• InChiKey: BXNPNIHSCGFACU-FPLPWBNLSA-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：

  (Z)-2-butene-1,4-diyl-bis(mesitylenesulfonate) 、 N,N'-bis(mesitylenesulfonyl)-N-ethyl-1,3-diaminopropane 在 sodium hydride 作用下， 生成 (Z)-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：

  1,4-丁烯二醇 以77的产率得到(Z)-2-butene-1,4-diyl-bis(mesitylenesulfonate)
  参考文献：
  名称：

  J. Med. Chem. 1998, 41, 4723-4732

  摘要：

  DOI：

文献信息

• 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。
• Conformationally Restricted Analogues of ¹<i>N</i>,¹⁴<i>N</i>-Bisethylhomospermine (BE-4-4-4):  Synthesis and Growth Inhibitory Effects on Human Prostate Cancer Cells
  作者：Aldonia Valasinas、Aparajita Sarkar、Venodhar K. Reddy、Laurence J. Marton、Hirak S. Basu、Benjamin Frydman

  DOI：10.1021/jm000309t

  日期：2001.2.1

  Twelve analogues of N-1,N-14-bisethylhomospermine (BE-4-4-4) with restricted conformations were synthesized in the search for cancer chemotherapeutic agents with higher cytotoxic activities and lower systemic toxicities than BE-4-4-4. The central butane segment of BE-4-4-4 was replaced with a 1,2-substituted cyclopropane ring, a 1,2-substituted cyclobutane ring, and a 2-butene residue. In each case, the cis/trans-isomeric pair was synthesized. Cis-monounsaturation(s) was also introduced at the outer butane segment(s) of BE-4-4-4. The two possible cis-dienes and a cis-triene formally derived from the tetraazaeicosane skeleton of BE-4-4-4 were also prepared. Four cultured human prostate cancer cell lines (LnCap, DU145, DuPro, and PC-3) were treated with the new tetramines to examine their effects on cell growth with a MTT assay. One representative cell line (DuPro) was selected to further study the cellular uptake of the novel tetramines, their effects on intracellular polyamine pools, and their cytotoxicity. All tetramines entered the cells, reduced cellular putrescine and spermidine pools while exerting only a small effect on the spermine pool, inhibited cell growth, and killed 2-3 log; of cells after 6 days of treatment at 10 muM. Four new tetramines, the two cyclopropyl isomers, the trans-cyclobutyl isomer, and the (5Z)-tetraazaeicosene, were more cytotoxic than their saturated counterpart (BE-4-4-4). Their cytotoxicity, however, could not be correlated either with their cellular uptake or with their ability to deplete intracellular polyamine pools. We attribute their cytotoxicity to their specific molecular structures. The cytotoxicity was markedly reduced when the central butane segment was deprived of its rotational freedom by replacing it with a double bond. Introduction of a triple bond or a benzene-1,2-dimethyl residue at the central segment of the polyamine chain, led to complete loss of biological activity. The conformationally restricted alicyclic derivatives were not only more cytotoxic than was the freely rotating BE-4-4-4 by several orders of magnitude but also had much lower systemic toxicities than the latter. Thus, we obtained new tetramines with a wider therapeutic window than BE-4-4-4.
• Long-chain polyamines (oligoamines) exhibit strong cytotoxicities against human prostate cancer cells
  作者：Aldonia Valasinas、Venodhar K Reddy、Andrei V Blokhin、Hirak S Basu、Subhra Bhattacharya、Aparajita Sarkar、Laurence J Marton、Benjamin Frydman

  DOI：10.1016/s0968-0896(03)00453-x

  日期：2003.9

  N-alpha,N-omega-bis(ethyl) octamine SL-11160, decamine SL-11159, dodecamine SL-11226, and tetradecamine SL-11175 were chemically synthesized. We called this class of compounds 'oligoamines'. In these compounds, each -NH2+ residue is separated by four CH2 residues. trans-Unsaturation was also introduced into the center of the oligoamine chain resulting in the trans-octamine SL-11158, trans-decamine SL-11144, trans-dodecamine SL-11172 and trans-tetradecamine SL-11227. cis-Unsaturation gave the cisoctamine SL-11157 and cis-decamine SL-11150. When assayed for their growth inhibitory effect against four human prostate cancer cell lines LnCap, DU-145, DuPro, and PC-3 by a MTT assay, the ID50 values were less than 1 muM in all four cell lines. On day 6 of treatment, 2 muM SL-11159, SL-11144 and SL-11175 killed over five logs of DuPro cells while SL-11172 killed over four logs as determined by a colony forming efficiency (CFE) assay. In addition, SL-11159, SL-11226 and SL-11227 killed four logs of PC-3 cells. PC-3 cells are generally resistant to shorter chain polyamine analogues. Such a level of cytotoxicity in any of the prostate tumor cell lines has not been observed for any other polyamine analogues tested thus far. The DU-145 cell line was too sensitive to oligoamines to perform a CFE analysis and the DuPro cell line was too sensitive to SL-11227 treatment to obtain reproducible CFE data. Interestingly, all 10 oligoamines were efficient DNA aggregators in a cell-free system and their cytotoxicities generally parallel their capacities to aggregate DNA. (C) 2003 Elsevier Ltd. All rights reserved.
• Conformationally Restricted Analogues of ¹<i>N</i>,¹²<i>N</i>-Bisethylspermine:  Synthesis and Growth Inhibitory Effects on Human Tumor Cell Lines
  作者：Venodhar K. Reddy、Aldonia Valasinas、Aparajita Sarkar、Hirak S. Basu、Laurence J. Marton、Benjamin Frydman

  DOI：10.1021/jm980172v

  日期：1998.11.1

  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.
• J. Med. Chem. 1998, 41, 4723-4732
  作者：

  DOI：——

  日期：——