(21E)-3β-hydroxy-21-(2'-fluorobenzylidene)pregn-5-en-20-one | 1365727-72-5

• 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: (21E)-3β-hydroxy-21-(2'-fluorobenzylidene)pregn-5-en-20-one
• 英文别名: (E)-3-(2-fluorophenyl)-1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]prop-2-en-1-one
• CAS: 1365727-72-5
• 化学式: C₂₈H₃₅FO₂
• 分子量: 422.583
• InChiKey: GESVBYCEXHOSJK-SDVMSRBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (21E)-3β-hydroxy-21-(2'-fluorobenzylidene)pregn-5-en-20-one 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以90%的产率得到(E)-3-(2-fluorophenyl)-1-[(1S,2R,5S,7R,9S,11S,12S,15S,16S)-5-hydroxy-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadecan-15-yl]prop-2-en-1-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 21-arylidenepregnenolone derivatives as neuroprotective agents

  摘要：

  A series of 21-arylidenepregnenolone derivatives and their corresponding epoxides were synthesized. The neuroprotective effects of these steroidal compounds against amyloid-beta(5-35)(A beta(25-35))- and hydrogen peroxide (H2O2)-induced neurotoxicity in PC12 cells, and oxygen-glucose deprivation (OGD)-induced neurotoxicity in SH-SY5Y cells were evaluated. The bioassay results indicated that several 3b-pregn-21-benzylidene-20-one derivatives displayed potent in vitro neuroprotective effects in different screening models, for example, compounds 2b, 3a, 3b, and 3s showing significant activities against A beta(25-35)-induced neurotoxicity in PC12 cells, 2b showing significant activities against H2O2-induced neurotoxicity in PC12 cells, and 2g, 3b, and 3e showing potent protection against OGD insult. The results suggested that introduction of an arylidene group into steroidal nucleus played an important role in neuroprotective activity, while the formation of epoxy group at C-5,6 could be also important for the neuroprotective activity in some degree. The pharmacological data reported here are helpful for the design of novel steroidal neuroprotective candidates. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.103
• 作为产物：
  描述：

  孕烯醇酮 、 2-氟苯甲醛 在 aluminum oxide 、 potassium fluoride 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以92%的产率得到(21E)-3β-hydroxy-21-(2'-fluorobenzylidene)pregn-5-en-20-one
  参考文献：
  名称：

  Efficient synthesis of novel antiproliferative steroidal spirooxindoles via the [3+2] cycloaddition reactions of azomethine ylides

  摘要：

  A series of novel steroidal spirooxindoles 3a-h were synthesized from pregnenolone in a high regioselective manner using the 1,3-dipolar cycloaddition as the key step. This protocol resulted in the formation of two C-C bonds, one C-N bond and the creation of one pyrrolidine ring and three contiguous stereocenters in a single operation. Biological evaluation showed that these synthesized steroidal spirooxindoles exhibited moderate to good antiproliferative activity against the tested cell lines and some of them were more potent than 5-FU. Among them, compounds 3e and 3f displayed the best antiproliferative activity against MCF-7 cells with the IC50 values of 4.0 and 3.9 mu M, respectively. Flow cytometry analysis demonstrated that compound 3d caused the cellular apoptosis and cell cycle arrest at G2/M phase in a concentration-dependent manner. Docking results indicated that compound 3d fitted well into the MDM2 active site 1RV1 by interacting with Lys94 and Thr101 residues. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2015.08.003

文献信息

• Synthesis and biological evaluation of 21-arylidenepregnenolone derivatives as neuroprotective agents
  作者：Cheng-Shi Jiang、Xian-Jun Guo、Jing-Xu Gong、Ting-Ting Zhu、Hai-Yan Zhang、Yue-Wei Guo

  DOI：10.1016/j.bmcl.2012.01.103

  日期：2012.3

  A series of 21-arylidenepregnenolone derivatives and their corresponding epoxides were synthesized. The neuroprotective effects of these steroidal compounds against amyloid-beta(5-35)(A beta(25-35))- and hydrogen peroxide (H2O2)-induced neurotoxicity in PC12 cells, and oxygen-glucose deprivation (OGD)-induced neurotoxicity in SH-SY5Y cells were evaluated. The bioassay results indicated that several 3b-pregn-21-benzylidene-20-one derivatives displayed potent in vitro neuroprotective effects in different screening models, for example, compounds 2b, 3a, 3b, and 3s showing significant activities against A beta(25-35)-induced neurotoxicity in PC12 cells, 2b showing significant activities against H2O2-induced neurotoxicity in PC12 cells, and 2g, 3b, and 3e showing potent protection against OGD insult. The results suggested that introduction of an arylidene group into steroidal nucleus played an important role in neuroprotective activity, while the formation of epoxy group at C-5,6 could be also important for the neuroprotective activity in some degree. The pharmacological data reported here are helpful for the design of novel steroidal neuroprotective candidates. (C) 2012 Elsevier Ltd. All rights reserved.
• Efficient synthesis of novel antiproliferative steroidal spirooxindoles via the [3+2] cycloaddition reactions of azomethine ylides
  作者：Bin Yu、Xiao-Nan Sun、Xiao-Jing Shi、Ping-Ping Qi、Yi-Chao Zheng、De-Quan Yu、Hong-Min Liu

  DOI：10.1016/j.steroids.2015.08.003

  日期：2015.10

  A series of novel steroidal spirooxindoles 3a-h were synthesized from pregnenolone in a high regioselective manner using the 1,3-dipolar cycloaddition as the key step. This protocol resulted in the formation of two C-C bonds, one C-N bond and the creation of one pyrrolidine ring and three contiguous stereocenters in a single operation. Biological evaluation showed that these synthesized steroidal spirooxindoles exhibited moderate to good antiproliferative activity against the tested cell lines and some of them were more potent than 5-FU. Among them, compounds 3e and 3f displayed the best antiproliferative activity against MCF-7 cells with the IC50 values of 4.0 and 3.9 mu M, respectively. Flow cytometry analysis demonstrated that compound 3d caused the cellular apoptosis and cell cycle arrest at G2/M phase in a concentration-dependent manner. Docking results indicated that compound 3d fitted well into the MDM2 active site 1RV1 by interacting with Lys94 and Thr101 residues. (C) 2015 Elsevier Inc. All rights reserved.