3,8,13,18-tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraazaheneicosanecyanide | 304863-14-7

• 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: 3,8,13,18-tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraazaheneicosanecyanide
• 英文别名: N-[4-[4-[4-[3-cyanopropyl-(2,4,6-trimethylphenyl)sulfonylamino]butyl-(2,4,6-trimethylphenyl)sulfonylamino]butyl-(2,4,6-trimethylphenyl)sulfonylamino]butyl]-N-ethyl-2,4,6-trimethylbenzenesulfonamide
• CAS: 304863-14-7
• 化学式: C₅₄H₇₉N₅O₈S₄
• 分子量: 1054.51
• InChiKey: KTFUZHBTBCFMQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.5
• 重原子数：
  71
• 可旋转键数：
  27
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  207
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  3,8,13,18-tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraazaheneicosanecyanide 在 platinum(IV) oxide sodium hydroxide 、 氢气 作用下， 以 乙醇 、 氯仿 为溶剂， 22.0 ℃ 、310.26 kPa 条件下， 反应 23.0h， 生成 1,5,10,15,20-pentakis(mesitylenesulfonyl)-1,5,10,15,20-pentaazatricosane
  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：

  5,10,15-tris(mesitylenesulfonyl)-5,10,15-triaza-1-heptadecylamine 在 sodium hydroxide 、 sodium hydride 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 3,8,13,18-tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraazaheneicosanecyanide
  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

文献信息

• [EN] PORPHYRIN-POLYAMINE CONJUGATES FOR CANCER THERAPY<br/>[FR] CONJUGUE DE PORPHYRINE-POLYAMINE POUR LA CANCEROTHERAPIE
  申请人：SLIL BIOMEDICAL CORP

  公开号：WO2004002991A1

  公开（公告）日：2004-01-08

  Porphyrin-polyamine conjugate compounds are disclosed which have anticancer and antitumor effects. The porphyrin moiety selectively localizes in tumors, while the polyamine moiety serves as a cytotoxic agent. Methods of making and using the porphyrin-polyamine conjugate compounds are also disclosed.

  揭示了具有抗癌和抗肿瘤效果的卟啉-聚胺共轭化合物。卟啉基团选择性地定位在肿瘤中，而聚胺基团作为细胞毒性剂。还公开了制备和使用卟啉-聚胺共轭化合物的方法。
• Cyclopropane-Containing Polyamine Analogues Are Efficient Growth Inhibitors of a Human Prostate Tumor Xenograft in Nude Mice
  作者：Benjamin Frydman、Andrei V. Blokhin、Sara Brummel、George Wilding、Yulia Maxuitenko、Aparajita Sarkar、Subhra Bhattacharya、Dawn Church、Venodhar K. Reddy、John A. Kink、Laurence J. Marton、Aldonia Valasinas、Hirak S. Basu

  DOI：10.1021/jm030175u

  日期：2003.10.1

  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.