A-105972 | 343346-07-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: A-105972
• 英文别名: 1,3,4-Oxadiazole, 3-acetyl-5-(4-amino-3-methylphenyl)-2,3-dihydro-2-(3,4,5-trimethoxyphenyl)-；1-[5-(4-amino-3-methylphenyl)-2-(3,4,5-trimethoxyphenyl)-2H-1,3,4-oxadiazol-3-yl]ethanone
• CAS: 343346-07-6
• 化学式: C₂₀H₂₃N₃O₅
• 分子量: 385.42
• InChiKey: MDKFBOKRJCLOEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  95.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氨基-3-甲基苯甲酸甲酯 在 4-二甲氨基吡啶 、 硫酸 、 溶剂黄146 、 苯硫酚 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.25h， 生成 A-105972
  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

• 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.