(9S)-9-ethyl-9-hydroxy-1-[2-(4-morpholino)ethyl]-1H,12H-pyrano[3",4":6',7']-indolizino[1',2':6,5]pyrido[4,3,2-de]quinazoline-10,13(9H,15H)dione hydrochloride | 1151915-59-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: (9S)-9-ethyl-9-hydroxy-1-[2-(4-morpholino)ethyl]-1H,12H-pyrano[3",4":6',7']-indolizino[1',2':6,5]pyrido[4,3,2-de]quinazoline-10,13(9H,15H)dione hydrochloride
• 英文别名: (10S)-10-ethyl-10-hydroxy-23-(2-morpholin-4-ylethyl)-8-oxa-4,15,21,23-tetrazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16(24),17,19,21-octaene-5,9-dione;hydrochloride
• CAS: 1151915-59-1
• 化学式: C₂₇H₂₇N₅O₅*ClH
• 分子量: 538.003
• InChiKey: IVPZUFJPOMNJIV-YCBFMBTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.31
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (9S)-9-acetoxy-9-ethyl-1-[2-(4-morpholino)ethyl]-1H,12H-pyrano[3'',4'':6',7']indolizino[1',2':6,5]pyrido[4,3,2-de]quinazoline-10,13(9H,15H)-dione 在 肼 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 生成 (9S)-9-ethyl-9-hydroxy-1-[2-(4-morpholino)ethyl]-1H,12H-pyrano[3",4":6',7']-indolizino[1',2':6,5]pyrido[4,3,2-de]quinazoline-10,13(9H,15H)dione hydrochloride
  参考文献：
  名称：

  合成具有改进抗肿瘤活性的喜树碱类似物

  摘要：

  基于拓扑异构酶I（Topo I）/ DNA /喜树碱三元复合物的3D结构，设计并合成了含有环am，尿素或硫脲部分的新型六环喜树碱类似物。由9-硝基喜树碱经7，9-二氨基喜树碱衍生物作为关键中间体制备类似物。其中，7c在人类癌症异种移植模型中以最大耐受剂量表现出优于CPT-11的体内抗肿瘤活性，尽管其在体外的抗增殖活性可与SN-38媲美。

  DOI：

  10.1016/j.bmcl.2009.02.031

文献信息

• Novel hexacyclic compounds
  申请人：——

  公开号：US20030144304A1

  公开（公告）日：2003-07-31

  The present invention relates to hexacyclic compound of the formula [1], 1 wherein Z, R 3 and R 4 are as identified therein, and pharmaceutically acceptable salts thereof. These compounds are useful in the treatment of cell proliferative disorders.

  本发明涉及公式［1］中的六环化合物，其中Z、R3和R4如所述，以及其药用可接受的盐。这些化合物可用于治疗细胞增殖性疾病。
• Novel Water-Soluble Prodrugs
  申请人：Umeda Isao

  公开号：US20080015157A1

  公开（公告）日：2008-01-17

  An objective of the present invention is to provide water-soluble prodrugs that can be administered parenterally, and which show excellent water solubility and small interspecies or individual differences and are rapidly converted to the active form by chemical conversion. This invention provides water-soluble prodrugs represented by formula (1), or pharmaceutically acceptable salts, or hydrates or solvates thereof, (wherein, R 1 represents a hydrogen atom, or C1-C6 alkyl group; W represents a divalent group comprising a tertiary amino group or sulfonyl group; and Y represents a residue of a compound represented by Y—OH comprising an alcoholic hydroxyl group).

  本发明的目的是提供可经由肌肉注射给药的水溶性前药，其具有优异的水溶性、小的种间或个体差异，并且可通过化学转化迅速转化为活性形式。本发明提供了由式(1)表示的水溶性前药，或其药学上可接受的盐、水合物或溶剂化物，其中R1代表氢原子或C1-C6烷基；W代表包含三级胺基或磺酰基的二价基团；Y代表由Y-OH表示的化合物的残基，该化合物包括醇羟基。
• Novel process for the preparation of hexacyclic compounds
  申请人：Fukuda Hiroshi

  公开号：US20060178376A1

  公开（公告）日：2006-08-10

  This invention relates to novel processes for the preparation of compounds of the formula [1], wherein R1, R2, R3 and R4 are as defined in the claims and description as well as pharmaceutically acceptable salts thereof. The compounds of the formula [1] are hexacyclic compounds having potent anti-tumor activity.

  本发明涉及一种制备公式[1]化合物的新型工艺，其中R1，R2，R3和R4如权利要求和说明书中所定义，并且它们的药学上可接受的盐。公式[1]化合物是具有强大的抗肿瘤活性的六环化合物。
• Preventive or Therapeutic Agents for Pancreatic Cancer, Ovarian Cancer, or Liver Cancer Comprising a Novel Water-Soluble Prodrug
  申请人：Umeda Isao

  公开号：US20090118271A1

  公开（公告）日：2009-05-07

  Preventive or therapeutic agents for pancreatic cancer, ovarian cancer, or liver cancer of the present invention comprise a water-soluble prodrug represented by formula 1 described below, or a pharmaceutically acceptable salt, or a hydrate or solvate of the prodrug or pharmaceutically acceptable salt, (wherein, R 1 represents a hydrogen atom, or a C1-C6 alkyl group; W represents a divalent group comprising a tertiary amino group or a divalent group comprising a sulfonyl group, and Y represents a residue of a compound represented by Y—OH comprising an alcoholic hydroxyl group, wherein said Y—OH is a camptothecin, a taxane, or an anticancer nucleotide).

  本发明的胰腺癌、卵巢癌或肝癌的预防或治疗剂包括以下式子1所描述的水溶性前药，或其药学上可接受的盐、水合物或溶剂化物（其中，R1代表氢原子或C1-C6烷基；W代表含有三级胺基的二价基团或含有磺酰基的二价基团，而Y代表一个化合物残基，该化合物残基由含有醇羟基的Y—OH所表示，其中所述的Y—OH是一种喜树碱、紫杉醇或抗癌核苷酸）。
• Novel Process for the Preparation of Hexacyclic Compounds
  申请人：FUKUDA HIROSHI

  公开号：US20090312554A1

  公开（公告）日：2009-12-17

  This invention relates to novel processes for the preparation of compounds of the formula [1], wherein R 1 , R 2 , R 3 and R 4 are as defined in the claims and description as well as pharmaceutically acceptable salts thereof. The compounds of the formula [ 1 ] are hexacyclic compounds having potent anti-tumor activity.

  本发明涉及一种新的制备式[1]化合物的方法，其中R1、R2、R3和R4如权利要求和说明书中所定义，以及其药学上可接受的盐。式[1]化合物是具有强效抗肿瘤活性的六环化合物。