radicicol (Z)-6-{O-[((4-(diethylamino)phenyl)carbamoyl)methyl]oxime}

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: radicicol (Z)-6-{O-[((4-(diethylamino)phenyl)carbamoyl)methyl]oxime}
• 英文别名: 2-[(Z)-[(4R,6R,8R,9Z,11E)-16-chloro-17,19-dihydroxy-4-methyl-2-oxo-3,7-dioxatricyclo[13.4.0.06,8]nonadeca-1(15),9,11,16,18-pentaen-13-ylidene]amino]oxy-N-[4-(diethylamino)phenyl]acetamide
• 化学式: C₃₀H₃₄ClN₃O₇
• 分子量: 584.069
• InChiKey: YNDANYSKUQCMHH-WCMCAFRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  133
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N,N-二乙基对苯二胺 、 KF29156 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 radicicol (E)-6-{O-[((4-(diethylamino)phenyl)carbamoyl)methyl]oxime} 、 radicicol (Z)-6-{O-[((4-(diethylamino)phenyl)carbamoyl)methyl]oxime}
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Novel O-Carbamoylmethyloxime Derivatives of Radicicol

  摘要：

  Radicicol (1), a macrocyclic antifungal antibiotic, is the lead compound of a novel class of heat shock protein 90 (Hsp90) inhibitors that result in the inhibition or degradation of Hsp90-associated proteins, such as v-src and Raf-1 kinases. New O-carbamoylmethyloxime derivatives of 1 were synthesized and evaluated for their in vitro antiproliferative activities against v-src-and K-ras-transformed cells and for their inhibitory activity against v-src tyrosine kinase. O-(Piperidinocarbonyl)methyloxime 9b, one of the most potent of these derivatives, exhibited more potent antiproliferative activity than 1 and its hydroxime KF25706 (2) and had an IC50 of 25 nM for the inhibition of v-src kinase activity. Compound 9b was also found to decrease the Raf-1 protein level of KNRK5.2 cells. Furthermore, compound 9b exhibited significant antitumor activity when tested against MX-1 and A431 xenografts in nude mice.

  DOI：

  10.1021/jm030110r

文献信息

• Synthesis and Antitumor Activity of Novel <i>O</i>-Carbamoylmethyloxime Derivatives of Radicicol
  作者：Yoji Ikuina、Nobuyoshi Amishiro、Mayumi Miyata、Hiroaki Narumi、Harumi Ogawa、Tadakazu Akiyama、Yukimasa Shiotsu、Shiro Akinaga、Chikara Murakata

  DOI：10.1021/jm030110r

  日期：2003.6.1

  Radicicol (1), a macrocyclic antifungal antibiotic, is the lead compound of a novel class of heat shock protein 90 (Hsp90) inhibitors that result in the inhibition or degradation of Hsp90-associated proteins, such as v-src and Raf-1 kinases. New O-carbamoylmethyloxime derivatives of 1 were synthesized and evaluated for their in vitro antiproliferative activities against v-src-and K-ras-transformed cells and for their inhibitory activity against v-src tyrosine kinase. O-(Piperidinocarbonyl)methyloxime 9b, one of the most potent of these derivatives, exhibited more potent antiproliferative activity than 1 and its hydroxime KF25706 (2) and had an IC50 of 25 nM for the inhibition of v-src kinase activity. Compound 9b was also found to decrease the Raf-1 protein level of KNRK5.2 cells. Furthermore, compound 9b exhibited significant antitumor activity when tested against MX-1 and A431 xenografts in nude mice.