SL-11098

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: SL-11098
• 英文别名: 3,8,13,18-tetraaza-10,11-[(Z)-1,2-cyclopropyl]eicosane；N-ethyl-N'-[[(1S,2R)-2-[[4-(ethylamino)butylamino]methyl]cyclopropyl]methyl]butane-1,4-diamine
• 化学式: C₁₇H₃₈N₄
• 分子量: 298.516
• InChiKey: BAOFSMLABBUBJP-CALCHBBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  48.1
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,8,13,18-tetrakis(mesitylenesulfonyl)-10,11-[(Z)-1,2-cyclopropyl]-3,8,13,18-tetraazaeicosane 在 氢溴酸 、 溶剂黄146 、 苯酚 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 SL-11098
  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

• PHARMACEUTICAL FOR ORAL DELIVERY COMPRISING MGBG AND METHODS OF TREATING DISEASE
  申请人：McKearn John

  公开号：US20110112199A1

  公开（公告）日：2011-05-12

  Disclosed herein are new oral pharmaceutical compositions of MGBG and related polyamine analogs, polyamine biosynthesis inhibitors, polyamine inhibitors of AMD-I and regulators of osteopontin, and their application for the treatment of disease.
• METHODS AND COMPOSITIONS FOR TREATMENT OF DEMYELINATING DISEASES
  申请人：PATHOLOGICA LLC

  公开号：US20150359761A1

  公开（公告）日：2015-12-17

  Disclosed herein are new oral pharmaceutical compositions of SAMDC inhibitors, polyamine analogs, and polyamine biosynthesis inhibitors, and their application for the treatment of conditions including demyelinating diseases, autoimmune disorders affecting the nervous system, and other neurodegenerative conditions.
• US8258186B2
  申请人：——

  公开号：US8258186B2

  公开（公告）日：2012-09-04
• [EN] PHARMACEUTICAL FOR ORAL DELIVERY COMPRISING MGBG AND METHODS OF TREATING DISEASE<br/>[FR] PRODUIT PHARMACEUTIQUE POUR ADMINISTRATION PAR VOIE ORALE COMPRENANT MGBG ET PROCÉDÉS DE TRAITEMENT DE MALADIE
  申请人：PATHOLOGICA LLC

  公开号：WO2011009039A2

  公开（公告）日：2011-01-20

  Disclosed herein are new oral pharmaceutical compositions of MGBG and related polyamine analogs, polyamine biosynthesis inhibitors, polyamine inhibitors of AMD-I and regulators of osteopontin, and their application for the treatment of disease.
• [EN] METHODS AND COMP0STIONS FOR TREATMENT OF DEMYELINATING DISEASES<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR LE TRAITEMENT DE MALADIES DE DÉMYÉLINISATION
  申请人：PATHOLOGICA LLC

  公开号：WO2014110154A1

  公开（公告）日：2014-07-17

  Disclosed herein are new oral pharmaceutical compositions of SAMDC inhibitors, polyamine analogs, and polyamine biosynthesis inhibitors, and their application for the treatment of conditions including demyelinating diseases, autoimmune disorders affecting the nervous system, and other neurodegenerative conditions.