N-(3-(9-fluorenylmethoxycarbonyl)amino-4-methoxybenzoyl)-1-(3,4,5-trimethoxyphenyl)-2-aminoethanol | 256935-70-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 英文名称: N-(3-(9-fluorenylmethoxycarbonyl)amino-4-methoxybenzoyl)-1-(3,4,5-trimethoxyphenyl)-2-aminoethanol
• 英文别名: 9H-fluoren-9-ylmethyl N-[5-[[2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]carbamoyl]-2-methoxyphenyl]carbamate
• CAS: 256935-70-3
• 化学式: C₃₄H₃₄N₂O₈
• 分子量: 598.653
• InChiKey: KOXLWICVBRGVHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(3-(9-fluorenylmethoxycarbonyl)amino-4-methoxybenzoyl)-1-(3,4,5-trimethoxyphenyl)-2-aminoethanol 在 methoxycarbonylsulfamoyl-triethylammmonium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以97%的产率得到{2-Methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-oxazol-2-yl]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester
  参考文献：
  名称：

  New Antimitotic Agents with Activity in Multi-Drug-Resistant Cell Lines and in Vivo Efficacy in Murine Tumor Models

  摘要：

  During a screen for compounds that could inhibit cell proliferation, a series of new tubulin-binding compounds was identified with the discovery of oxadiazoline 1 (A-105972). This compound showed good cytotoxic activity against non-multi-drug-resistant and multi-drug-resistant cancer cell lines, but its utility in vivo was limited by a short half-life. Medicinal chemistry efforts led to the discovery of indolyloxazoline 22g (A-259745), which maintained all of the in vitro activity seen with oxadiazoline 1, but also demonstrated a better pharmacokinetic profile, and dose-dependent in vivo activity. Over a 28 day study, indolyloxazoline 22g increased the life span of tumor-implanted mice by up to a factor of 3 upon oral dosing. This compound, and others of its structural class, may prove to be useful in the development of new chemotherapeutic agents to treat human cancers.

  DOI：

  10.1021/jm010231w
• 作为产物：
  描述：

  (9H-芴-9-基)甲基 2,5-二氧代吡咯烷-1-羧酸 在 N-甲基吗啉 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 18.0h， 生成 N-(3-(9-fluorenylmethoxycarbonyl)amino-4-methoxybenzoyl)-1-(3,4,5-trimethoxyphenyl)-2-aminoethanol
  参考文献：
  名称：

  New Antimitotic Agents with Activity in Multi-Drug-Resistant Cell Lines and in Vivo Efficacy in Murine Tumor Models

  摘要：

  During a screen for compounds that could inhibit cell proliferation, a series of new tubulin-binding compounds was identified with the discovery of oxadiazoline 1 (A-105972). This compound showed good cytotoxic activity against non-multi-drug-resistant and multi-drug-resistant cancer cell lines, but its utility in vivo was limited by a short half-life. Medicinal chemistry efforts led to the discovery of indolyloxazoline 22g (A-259745), which maintained all of the in vitro activity seen with oxadiazoline 1, but also demonstrated a better pharmacokinetic profile, and dose-dependent in vivo activity. Over a 28 day study, indolyloxazoline 22g increased the life span of tumor-implanted mice by up to a factor of 3 upon oral dosing. This compound, and others of its structural class, may prove to be useful in the development of new chemotherapeutic agents to treat human cancers.

  DOI：

  10.1021/jm010231w

文献信息

• Oxazoline antiproliferative agents
  申请人：Abbott Laboratories

  公开号：US06228868B1

  公开（公告）日：2001-05-08

  Compounds having Formula I are useful for treating cancer. Also disclosed are pharmaceutical compositions comprising compounds of Formula I, and methods of treating cancer in a mammal.

  具有化学式I的化合物对治疗癌症有用。还公开了包含化学式I化合物的药物组合物，以及在哺乳动物中治疗癌症的方法。
• US6228868B1
  申请人：——

  公开号：US6228868B1

  公开（公告）日：2001-05-08
• New Antimitotic Agents with Activity in Multi-Drug-Resistant Cell Lines and in Vivo Efficacy in Murine Tumor Models
  作者：Bruce G. Szczepankiewicz、Gang Liu、Hwan-Soo Jae、Andrew S. Tasker、Indrani W. Gunawardana、Thomas W. von Geldern、Stephen L. Gwaltney、J. Ruth Wu-Wong、Laura Gehrke、William J. Chiou、R. Bruce Credo、Jeffery D. Alder、Michael A. Nukkala、Nicolette A. Zielinski、Ken Jarvis、Karl W. Mollison、David J. Frost、Joy L. Bauch、Yu Hua Hui、Akiyo K. Claiborne、Qun Li、Saul H. Rosenberg

  DOI：10.1021/jm010231w

  日期：2001.12.1

  During a screen for compounds that could inhibit cell proliferation, a series of new tubulin-binding compounds was identified with the discovery of oxadiazoline 1 (A-105972). This compound showed good cytotoxic activity against non-multi-drug-resistant and multi-drug-resistant cancer cell lines, but its utility in vivo was limited by a short half-life. Medicinal chemistry efforts led to the discovery of indolyloxazoline 22g (A-259745), which maintained all of the in vitro activity seen with oxadiazoline 1, but also demonstrated a better pharmacokinetic profile, and dose-dependent in vivo activity. Over a 28 day study, indolyloxazoline 22g increased the life span of tumor-implanted mice by up to a factor of 3 upon oral dosing. This compound, and others of its structural class, may prove to be useful in the development of new chemotherapeutic agents to treat human cancers.