(21E)-3β-hydroxy-21-(4'-chlorobenzylidene)pregn-5-en-20-one | 1365727-53-2

• 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: (21E)-3β-hydroxy-21-(4'-chlorobenzylidene)pregn-5-en-20-one
• 英文别名: (2E)-3-(4-chlorophenyl)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3(β)-hydroxy-10,13-dimethyl-1H-cyclopenta[a]phenanthren-17(β)-yl)prop-2-en-1-one；(21E)-3β-hydroxy-21-(p-chlorobenzylidene)pregn-5-en-20-one；(E)-3-(4-chlorophenyl)-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: 1365727-53-2
• 化学式: C₂₈H₃₅ClO₂
• 分子量: 439.038
• InChiKey: MCQDPLIJIWZQHR-DEZCMFKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 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：
  2

反应信息

• 作为反应物：
  描述：

  (21E)-3β-hydroxy-21-(4'-chlorobenzylidene)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83%的产率得到(E)-3-(4-chlorophenyl)-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 、 4-氯肉桂醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以87%的产率得到(21E)-3β-hydroxy-21-(4'-chlorobenzylidene)pregn-5-en-20-one
  参考文献：
  名称：

  Synthesis of D-ring-substituted (5′R)- and (5′S)-17β-pyrazolinylandrostene epimers and comparison of their potential anticancer activities

  摘要：

  Various steroidal benzylidenes were synthetized from pregnenolone with benzaldehyde and p-substituted benzaldehydes. The resulting 17 beta-chalconyl derivatives of pregnenolone were reacted with hydrazine hydrate in acetic acid solution. Regardless of the starting material, the ring-closure reaction afforded (in contrast with the literature data) a mixture of two steroidal pyrazoline epimers. The epimers were critical isomer pairs, which could be separated only in their acetylated form; their structures were investigated by NMR techniques. The in vitro inhibition of rat testicular C-17,C-20-lyase activity and the antiproliferative effects on four human cancer cell lines were measured, and the results obtained from the two epimer series were compared. (C) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2012.02.001

文献信息

• A Nature-Inspired Design Yields a New Class of Steroids Against Trypanosomatids
  作者：Elena Aguilera、Cintya Perdomo、Alejandra Espindola、Ileana Corvo、Paula Faral-Tello、Carlos Robello、Elva Serna、Fátima Benítez、Rocío Riveros、Susana Torres、Ninfa I. Vera de Bilbao、Gloria Yaluff、Guzmán Alvarez

  DOI：10.3390/molecules24203800

  日期：——

  biological activity against Leishmania infantum, Leishmania amazonensis, and Trypanosoma cruzi in vitro and in vivo. We also assayed their genotoxicity and acute toxicity in vitro and in mice. The best compound, a steroidal thiosemicarbazone compound 8 (ID_1260) was active in vitro (IC50 200 nM) and in vivo (60% infection reduction at 50 mg/kg) in Leishmania and T. cruzi. It also has low toxicity in vitro and

  恰加斯病和利什曼病是被世界卫生组织认定为公共卫生问题的地方性原生动物疾病。这些疾病影响着世界各地的数百万人，但目前还没有有效和低成本的治疗方法。从不同的生物体（蜱、植物、真菌）中分离出具有抗微生物和抗寄生虫活性的不同类固醇分子。这些分子具有复杂的结构，使得从头合成极其困难。在这项工作中，我们受天然类固醇的启发，设计了具有抗寄生虫潜力的新的更简单的化合物，并合成了一系列 19 种甾体亚芳基酮和噻唑烷肼。我们在体外和体内探索了它们对婴儿利什曼原虫、亚马逊利什曼原虫和克氏锥虫的生物活性。我们还在体外和小鼠中测定了它们的遗传毒性和急性毒性。最好的化合物，甾体缩氨基硫脲化合物 8 (ID_1260) 在体外 (IC50 200 nM) 和体内 (50 mg/kg 时感染减少 60%) 在利什曼原虫和克氏锥虫中均有活性。它还具有体外和体内低毒性（LD50 > 2000 mg/kg）和无遗传毒性作用，是一种有前景的抗锥虫药物开发化合物。
• Synthesis, pharmacological evaluation and Molecular modelling studies of pregnenolone derivatives as inhibitors of human dihydrofolate reductase
  作者：Muhammad Bilal Tufail、Muhammad Aamir Javed、Muhammad Ikram、Mater H. Mahnashi、Bandar A. Alyami、Yahya S. Alqahtani、Abdul Sadiq、Umer Rashid

  DOI：10.1016/j.steroids.2021.108801

  日期：2021.4

  In current study, we synthesized chalcone derivatives (13a-c) via base-catalyzed Claisen-Schmidt condensation reaction. We further treated diamino compounds with synthesized chalcones to produce 3,4-dihydropyrimidin-2(1H)-one (18a-c), 3,4-dihydropyrimidin-2(1H)-thione (19a-c) and 2-aminopyrimidine (20a-c) derivatives of pregnenolone by cyclization reaction. Cell viability test of synthesized steroidal

  在当前的研究中，我们通过碱催化的Claisen-Schmidt缩合反应合成了查尔酮衍生物（13a-c）。我们用合成的查耳酮进一步处理了二氨基化合物，以产生3,4-dihydropyrimidin-2（1H）-one（18a-c），3,4-dihydropyrimidin-2-2（1H）-硫酮（19a-c）和2-aminopyrimidine（ 20a-c）孕烯醇酮的衍生物通过环化反应。使用（4,5-二甲基噻唑-2- yl）-2,5-二苯基溴化四氮唑（MTT），测定。进一步评估化合物对重组人DHFR（rhDHFR）的抑制潜力。所有化合物均显示出从低微摩尔到亚微摩尔范围的活性。IC50值为180 nM的化合物20b成为对抗rhDHFR的最有效化合物。还通过对接模拟研究了新合成的孕烯醇酮衍生物与hDHFR和雌激素受体α（ERα）的相互作用。hDHFR抑制的总体结果表明，这些类似物可以进一步优化和开发为有效的抗癌药。
• 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.
• Benzylidine pregnenolones and their oximes as potential anticancer agents: Synthesis and biological evaluation
  作者：Abid H. Banday、S.M.M. Akram、Shameem A. Shameem

  DOI：10.1016/j.steroids.2014.03.010

  日期：2014.6

  The present study reveals the anticancer activity of benzylidine pregnenolones and their oxime derivatives. The synthesis of the analogs of both series is very simple and involves aldol condensation in the first step followed by nucleophillic addition of hydroxylamine across carbonyl in the second step. Quantitative yields of more than 80% are obtained in both the steps. All the compounds were tested for their cytotoxic activities against a panel of six human cancer cell lines. Amongst all the compounds of both the series screened for their cytotoxic actvity, compound 3e, 3f and 4e are very potent especially against HCT-15 and MCF-7 cancer cell lines. (C) 2014 Elsevier Inc. All rights reserved.
• New biaryl-chalcone derivatives of pregnenolone via Suzuki–Miyaura cross-coupling reaction. Synthesis, CYP17 hydroxylase inhibition activity, QSAR, and molecular docking study
  作者：Najim A. Al-Masoudi、Rawaa A. Kadhim、Nabeel A. Abdul-Rida、Bahjat A. Saeed、Matthias Engel

  DOI：10.1016/j.steroids.2015.05.011

  日期：2015.9

  A new class of steroids is being synthesized for its ability to prevent intratumoral androgen production by inhibiting the activity of CYP17 hydroxylase enzyme. The scheme involved the synthesis of chalcone derivative of pregnenolone 5 which was further modified to the corresponding biaryl-chalcone pregnenolone analogs 16-25 using Suzuki-Miyaura cross-coupling reaction. The synthesized compounds were tested for activity using human CYP17 alpha hydroxylase expressed in Escherichia coli. Compounds 21 was the most active inhibitor in this series, with IC50 values of 0.61 mu M and selectivity profile of 88.7% inhibition of hydroxylase enzyme. Molecular docking study of 21 was performed and showed the hydrogen bonds and hydrophobic interaction with the amino acid residues of the active site of CYP17. (C) 2015 Elsevier Inc. All rights reserved.