bis(mesitylenesulfonyl) ester of 1,4-butanediol | 328260-27-1

• 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: bis(mesitylenesulfonyl) ester of 1,4-butanediol
• 英文别名: 1,4-bis(mesitylenesulfonyloxy)butane；4-(2,4,6-Trimethylphenyl)sulfonyloxybutyl 2,4,6-trimethylbenzenesulfonate
• CAS: 328260-27-1
• 化学式: C₂₂H₃₀O₆S₂
• 分子量: 454.609
• InChiKey: OMTLFFWGZDUPBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 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：
  104
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  bis(mesitylenesulfonyl) ester of 1,4-butanediol 、 N-ethyl N,N'-bis(mesitylenesulfonyl)-trans-1,2-bis(aminomethyl)cyclopropane 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以93%的产率得到N-ethyl-N-[[2-[[4-[[2-[[ethyl-(2,4,6-trimethylphenyl)sulfonylamino]methyl]cyclopropyl]methyl-(2,4,6-trimethylphenyl)sulfonylamino]butyl-(2,4,6-trimethylphenyl)sulfonylamino]methyl]cyclopropyl]methyl]-2,4,6-trimethylbenzenesulfonamide
  参考文献：
  名称：

  Cyclopropane-Containing Polyamine Analogues Are Efficient Growth Inhibitors of a Human Prostate Tumor Xenograft in Nude Mice

  摘要：

  Polyamine analogues 7, 10, 18, 27, and 32 containing cyclopropane rings were obtained by chemical synthesis. Their antineoplastic activities were assessed against the cultured human prostate tumor cell lines DU-145, DuPro, and PC-3. Decamines 32 and 27 exhibited variable levels of cytotoxicity against all three cell lines, while 7, 10, and 18 were efficacious against DU-145 and DuPro. Maximum tolerated doses (MTD) for all five compounds in a NCr-nu mouse model were determined at dosing schedules of q1d x 5 (ip) in two cycles with a break of 10 days between cycles. Their antitumor efficacies were then tested against DU-145 tumor xenografts in mice treated with all five agents at their respective MTDs. In addition, the efficacies of 7 and 10 against the same tumor xenograft were assessed at doses below their respective MTDs. In all experiments, administration began two weeks after tumor implantation. All compounds efficiently inhibited tumor growth for up to 50 days postimplantation, with negligible animal body weight loss. Tetramine 10 and hexamine 18 were the most efficient among the five analogues in arresting tumor growth. Tetramine 10 containing two cyclopropane rings had the lowest systemic toxicity as reflected in animal body weight loss. It was further assessed at a weekly administration regimen of (q1w x 4) in two cycles with a four-week break between the cycles. At this dosing schedule, 10 again efficiently arrested tumor growth with negligible effect on animal body weight. Tetramine 10 also arrested the growth of large tumors (ca. 2000 mm(3)) treated 66 days postimplantation. Studies on the metabolism of 10 showed that it accumulates in tumor within 6 h after the end of administration and reached a maximum level 72 h after cessation of dosing. Intracellular concentrations of 10 in liver and kidney were much smaller when compared to those in the tumor when measured 72 h after cessation of dosing. In liver and kidney, the deethyl metabolites of 10 accumulated over a 96 h period after cessation of dosing.

  DOI：

  10.1021/jm030175u
• 作为产物：
  描述：

  2,4,6-三甲基苯磺酰氯 、 1,4-丁二醇 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 4.0h， 以64%的产率得到bis(mesitylenesulfonyl) ester of 1,4-butanediol
  参考文献：
  名称：

  Conformationally Restricted Analogues of ¹N,¹⁴N-Bisethylhomospermine (BE-4-4-4):  Synthesis and Growth Inhibitory Effects on Human Prostate Cancer Cells

  摘要：

  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.

  DOI：

  10.1021/jm000309t

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。
• 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。
• US7491849B2
  申请人：——

  公开号：US7491849B2

  公开（公告）日：2009-02-17
• [EN] OLIGOAMINE COMPOUNDS AND DERIVATIVES THEREOF FOR CANCER THERAPY<br/>[FR] COMPOSES OLIGOAMINE ET LEURS DERIVES POUR LE TRAITEMENT DES CANCERS
  申请人：SLIL BIOMEDICAL CORP

  公开号：WO2003033455A1

  公开（公告）日：2003-04-24

  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.
• 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.