(2-chlorophenyl)methyl N-[4-[(2R,5S,8S,11S,14R)-5-[4-[3-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]butyl]-11,14-dibenzyl-13-methyl-8-(2-methylpropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]butyl]carbamate | 1374429-86-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: (2-chlorophenyl)methyl N-[4-[(2R,5S,8S,11S,14R)-5-[4-[3-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]butyl]-11,14-dibenzyl-13-methyl-8-(2-methylpropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]butyl]carbamate
• CAS: 1374429-86-3
• 化学式: C₆₆H₉₅ClN₁₀O₁₄S
• 分子量: 1320.06
• InChiKey: QQHMJNYWLXBPHX-AIZYYPCESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  92
• 可旋转键数：
  39
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  337
• 氢给体数：
  9
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  Fmoc-D-Lys(2-Cl-Z)-OH 在 N-羟基-7-氮杂苯并三氮唑 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.5h， 生成 (2-chlorophenyl)methyl N-[4-[(2R,5S,8S,11S,14R)-5-[4-[3-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]butyl]-11,14-dibenzyl-13-methyl-8-(2-methylpropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]butyl]carbamate
  参考文献：
  名称：

  An Hsp90 modulator that exhibits a unique mechanistic profile

  摘要：

  Described is the synthesis of two biotinylated derivatives of a cytotoxic macrocycle. Pull-down assays indicate that this macrocycle targets the N-middle domain of Hsp90. Untagged compound can effectively compete away tagged compound-Hsp90 protein complexes, confirming the binding specificity of the macrocycle for Hsp90. The macrocycle is similar in potency to other structurally-related analogs of Sansalvamide A (San A) and induces apoptosis via a caspase 3 mechanism. Unlike other San A derivatives, we show that the macrocycle does not inhibit binding between C-terminal client proteins and co-chaperones and Hsp90, suggesting that it has a unique mechanism of action. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.012

文献信息

• An Hsp90 modulator that exhibits a unique mechanistic profile
  作者：Deborah M. Ramsey、Jeanette R. McConnell、Leslie D. Alexander、Kaishin W. Tanaka、Chester M. Vera、Shelli R. McAlpine

  DOI：10.1016/j.bmcl.2012.03.012

  日期：2012.5

  Described is the synthesis of two biotinylated derivatives of a cytotoxic macrocycle. Pull-down assays indicate that this macrocycle targets the N-middle domain of Hsp90. Untagged compound can effectively compete away tagged compound-Hsp90 protein complexes, confirming the binding specificity of the macrocycle for Hsp90. The macrocycle is similar in potency to other structurally-related analogs of Sansalvamide A (San A) and induces apoptosis via a caspase 3 mechanism. Unlike other San A derivatives, we show that the macrocycle does not inhibit binding between C-terminal client proteins and co-chaperones and Hsp90, suggesting that it has a unique mechanism of action. (C) 2012 Elsevier Ltd. All rights reserved.