camtothecin-20-O-methylthiomethyl ether

• 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: camtothecin-20-O-methylthiomethyl ether
• 英文别名: (19S)-19-ethyl-19-(methylsulfanylmethoxy)-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione
• 化学式: C₂₂H₂₀N₂O₄S
• 分子量: 408.478
• InChiKey: DTUCSCKVNBVCRS-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  94
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  camtothecin-20-O-methylthiomethyl ether 以 phosphate buffer 、 二甲基亚砜 为溶剂， 反应 24.0h， 生成 (S)-2-(8-Hydroxymethyl-9-oxo-9,11-dihydro-indolizino[1,2-b]quinolin-7-yl)-2-methylsulfanylmethoxy-butyric acid
  参考文献：
  名称：

  20-O-Acylcamptothecin Derivatives:  Evidence for Lactone Stabilization

  摘要：

  Convincing UV and NMR spectrophotometric evidence is presented which demonstrates that at physiological pH, 7.4, 20-O-acyl derivatives of camptothecin (CPT) are substantially more stable in the lactone form than the 20-OH parent. Additionally, it was determined by HPLC analysis that the lactone ring of a 20-O-ether derivative of CPT underwent endocyclic ring opening at pR greater than or equal to 8.5, while the lactone ring of 20-O-acyl CPT derivatives remained unaffected. PEG (and other smaller alkyl) 20-O-acyl-CPT derivatives released native CPT at pH > 9.5, which arises from exocyclic cleavage, thus precluding isolation of any open CPT acyl PEG (or alkyl) carboxylate forms.

  DOI：

  10.1021/jo000221n
• 作为产物：
  描述：

  二甲基亚砜 、 喜树碱 以 乙酸酐 为溶剂， 反应 48.0h， 以83%的产率得到camtothecin-20-O-methylthiomethyl ether
  参考文献：
  名称：

  20-O-Acylcamptothecin Derivatives:  Evidence for Lactone Stabilization

  摘要：

  Convincing UV and NMR spectrophotometric evidence is presented which demonstrates that at physiological pH, 7.4, 20-O-acyl derivatives of camptothecin (CPT) are substantially more stable in the lactone form than the 20-OH parent. Additionally, it was determined by HPLC analysis that the lactone ring of a 20-O-ether derivative of CPT underwent endocyclic ring opening at pR greater than or equal to 8.5, while the lactone ring of 20-O-acyl CPT derivatives remained unaffected. PEG (and other smaller alkyl) 20-O-acyl-CPT derivatives released native CPT at pH > 9.5, which arises from exocyclic cleavage, thus precluding isolation of any open CPT acyl PEG (or alkyl) carboxylate forms.

  DOI：

  10.1021/jo000221n

文献信息

• [EN] WATER SOLUBLE PRODRUGS OF HINDERED ALCOHOLS OR PHENOLS<br/>[FR] PROMÉDICAMENTS SOLUBLES DANS L'EAU À FONCTION ALCOOL OU PHENOL MASQUÉ
  申请人：UNIV KANSAS

  公开号：WO2000008033A1

  公开（公告）日：2000-02-17

  The present invention is directed to novel water-soluble prodrugs of aliphatic or aromatic hindered hydroxyl group containing pharmaceuticals.

  本发明涉及一种新型水溶性脂肪族或芳香族受阻羟基含药物的前药。
• Water soluble prodrugs of hindered alcohols or phenols
  申请人：THE UNIVERSITY OF KANSAS

  公开号：EP1683803A1

  公开（公告）日：2006-07-26

  The present invention is directed to novel water-soluble prodrugs of aliphatic or aromatic hindered hydroxyl group containing pharmaceuticals.

  本发明涉及含脂肪族或芳香族受阻羟基药物的新型水溶性原药。
• Water soluble prodrugs of hindered alcohols
  申请人：University of Kansas

  公开号：US20010025035A1

  公开（公告）日：2001-09-27

  The present invention is directed to novel water-soluble prodrugs of aliphatic or aromatic hindered hydroxyl group containing pharmaceuticals.

  本发明涉及含脂肪族或芳香族受阻羟基药物的新型水溶性原药。
• WATER SOLUBLE PRODRUGS OF HINDERED PHENOLS
  申请人：THE UNIVERSITY OF KANSAS

  公开号：EP1102776B1

  公开（公告）日：2006-03-08
• WATER SOLUBLE PRODRUGS OF HINDERED ALCOHOLS OR PHENOLS
  申请人：THE UNIVERSITY OF KANSAS

  公开号：EP1102776A1

  公开（公告）日：2001-05-30