7-benzyl-3-(1-hydroxy-10-methyl-3-oxo-dodeca-1,4,6,8-tetraenyl)-9a-methyl-7H,9aH-furo[3,2-g]isoquinoline-2,9-dione | 1247024-40-3

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 7-benzyl-3-(1-hydroxy-10-methyl-3-oxo-dodeca-1,4,6,8-tetraenyl)-9a-methyl-7H,9aH-furo[3,2-g]isoquinoline-2,9-dione
• 英文别名: (9aR)-7-benzyl-3-[(1Z,4E,6E,8E)-1-hydroxy-10-methyl-3-oxododeca-1,4,6,8-tetraenyl]-9a-methylfuro[3,2-g]isoquinoline-2,9-dione
• CAS: 1247024-40-3
• 化学式: C₃₂H₃₁NO₅
• 分子量: 509.602
• InChiKey: QVHBUTWFXAVRBR-QTTCSEDVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-(benzylaminomethylene)-5-(2,3-dihydroxypropyl)-3-(1-hydroxy-10-methyl-3-oxo-dodeca-1,4,6,8-tetraenyl)-7a-methyl-6H,7aH-benzofuran-2,7-dione 在 sodium periodate 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 以55%的产率得到7-benzyl-3-(1-hydroxy-10-methyl-3-oxo-dodeca-1,4,6,8-tetraenyl)-9a-methyl-7H,9aH-furo[3,2-g]isoquinoline-2,9-dione
  参考文献：
  名称：

  Natural and semisynthetic azaphilones as a new scaffold for Hsp90 inhibitors

  摘要：

  A series of mold metabolites of Ascomycetes, structurally belonging to the class of azaphilones, were found to inhibit the heat shock protein Hsp90. In particular, bulgarialactone B was tested for its binding to Hsp90 using surface plasmon resonance and limited proteolysis assays and for its effects on Hsp90 client proteins expression in a series of human tumor cell lines. This compound showed high affinity for Hsp90, interacting with the 90-280 region of the N-terminal domain and down-regulated the Hsp90 client proteins Raf-1, survivin, Cdk4, Akt, and EGFR. Bulgarialactone B and other natural azaphilones showed antiproliferative activity in a panel of human tumor cell lines; their conversion into semisynthetic derivatives by reaction with primary amines increased the antiproliferative activity. Preliminary results indicated in vivo activity of bulgarialactone B against an ascitic ovarian carcinoma xenograft, thus supporting the therapeutic potential of this novel series of Hsp90 inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.068