(9H-fluoren-9-yl)methyl [(14S,17S,18R)-17-hydroxy-1-({(E)-[(8R,9S,13S,14S)-3-hydroxy-13-methyl-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-ylidene]amino}oxy)-14-isobutyl-2,13,16-trioxo-19-phenyl-6,9-dioxa-3,12,15-triazanonadecan-18-yl]carbamate | 1351169-44-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (9H-fluoren-9-yl)methyl [(14S,17S,18R)-17-hydroxy-1-({(E)-[(8R,9S,13S,14S)-3-hydroxy-13-methyl-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-ylidene]amino}oxy)-14-isobutyl-2,13,16-trioxo-19-phenyl-6,9-dioxa-3,12,15-triazanonadecan-18-yl]carbamate
• CAS: 1351169-44-2
• 化学式: C₅₇H₇₁N₅O₁₀
• 分子量: 986.218
• InChiKey: DHHFGHZGEYTCGU-MTXVEEGUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.93
• 重原子数：
  72.0
• 可旋转键数：
  23.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  206.14
• 氢给体数：
  6.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  (9H-fluoren-9-yl)methyl [(14S,17S,18R)-17-hydroxy-1-({(E)-[(8R,9S,13S,14S)-3-hydroxy-13-methyl-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-ylidene]amino}oxy)-14-isobutyl-2,13,16-trioxo-19-phenyl-6,9-dioxa-3,12,15-triazanonadecan-18-yl]carbamate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 十二硫醇 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以61%的产率得到(S)-2-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanamido]-N-[2-(2-{2-[2-({(E)-[(8R,9S,13S,14S)-3-hydroxy-13-methyl-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-ylidene]amino}oxy)acetamido]ethoxy}ethoxy)ethyl]-4-methylpentanamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of nuclear receptor-degradation inducers

  摘要：

  Compounds that regulate the function(s) of nuclear receptors (NRs) are useful for biological studies and as candidate therapeutic agents. Most such compounds are agonists or antagonists. On the other hand, we have developed specific protein degradation inducers, which we designated as SNIPERs (Specific and Nongenetic IAPs-dependent Protein ERasers), for selective degradation of target proteins. SNIPERs are hybrid molecules consisting of an appropriate ligand for the protein of interest, coupled to a ligand for inhibitor of apoptosis proteins (IAPs), which target the bound protein for polyubiquitination and proteasomal degradation. We considered that protein knockdown with SNIPERs would be a promising alternative approach for modulating NR function. In this study, we designed and synthesized degradation inducers targeting retinoic acid receptor (RAR), estrogen receptor (ER), and androgen receptor (AR). These newly synthesized RAR, ER, and AR SNIPERs, 9, 11, and 13, respectively, were confirmed to significantly reduce the levels of the corresponding NRs in live cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.041
• 作为产物：
  描述：

  雌酚酮 在 吡啶 、 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 二氯甲烷 、 水 为溶剂， 反应 17.0h， 生成 (9H-fluoren-9-yl)methyl [(14S,17S,18R)-17-hydroxy-1-({(E)-[(8R,9S,13S,14S)-3-hydroxy-13-methyl-7,8,9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-ylidene]amino}oxy)-14-isobutyl-2,13,16-trioxo-19-phenyl-6,9-dioxa-3,12,15-triazanonadecan-18-yl]carbamate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of nuclear receptor-degradation inducers

  摘要：

  Compounds that regulate the function(s) of nuclear receptors (NRs) are useful for biological studies and as candidate therapeutic agents. Most such compounds are agonists or antagonists. On the other hand, we have developed specific protein degradation inducers, which we designated as SNIPERs (Specific and Nongenetic IAPs-dependent Protein ERasers), for selective degradation of target proteins. SNIPERs are hybrid molecules consisting of an appropriate ligand for the protein of interest, coupled to a ligand for inhibitor of apoptosis proteins (IAPs), which target the bound protein for polyubiquitination and proteasomal degradation. We considered that protein knockdown with SNIPERs would be a promising alternative approach for modulating NR function. In this study, we designed and synthesized degradation inducers targeting retinoic acid receptor (RAR), estrogen receptor (ER), and androgen receptor (AR). These newly synthesized RAR, ER, and AR SNIPERs, 9, 11, and 13, respectively, were confirmed to significantly reduce the levels of the corresponding NRs in live cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.041