(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carbonyl isothiocyanate | 1135440-11-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carbonyl isothiocyanate
• CAS: 1135440-11-7
• 化学式: C₂₁H₂₇NOS
• 分子量: 341.517
• InChiKey: KQRMLEQDFXNDHZ-HMXCVIKNSA-N

物化性质

• 沸点：
  437.6±45.0 °C(predicted)
• 密度：
  1.12±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  61.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carbonyl isothiocyanate 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (1R,4aS,10aR)-N-[[4-[[4-[2,2-bis(diethoxyphosphoryl)ethylamino]phenyl]methyl]phenyl]carbamothioyl]-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxamide
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of dehydroabietic acid thiourea derivatives containing bisphosphonate moiety as an inducer of apoptosis

  摘要：

  A series of DHAA thiourea derivatives containing bisphosphonate moiety were designed and synthesized as potent antitumor agents. Structures of target molecules were confirmed using HR-MS,H-1 NMR and C-13 NMR and they exhibited potent anti-tumor activities against the SK-OV-3, BEL-7404, A549, HCT-116 and NCI-H460 tumor cell lines in vitro. Especially, compound 6e (IC50 = 1.79 +/- 0.43 mu M) exhibited the best anticancer activity against SK-OV-3 cell line. Its role as an inducer of apoptosis was investigated in this cell line by Annexin-V/PI binding assay and by following its capability for ROS generation, depolarization of mitochondrial transmembrane potential, activation of caspases and expression of pro- and anti-apoptotic proteins. Elevated level of ROS generation, activation of caspase-3, caspase-8, caspase-9, and Fas, higher expression of Bax, lower expression of Bcl-2, and increased level of Bax/Bcl-2 ratio identified 6e as a promising inducer of apoptosis that follows both of the mitochondria dependent pathway and the death receptor-mediated pathway. In addition, the cell cycle analysis indicated that compound 6e caused cell cycle arrest at G1 phase, induced apoptosis and led to cell death by increasing the proportion of sub G1 cells. Furthermore, molecular docking studies showed that 6e could bind to the ATP pocket sites. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.008
• 作为产物：
  描述：

  脱氢松香酸 在 氯化亚砜 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 6.5h， 生成 (1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carbonyl isothiocyanate
  参考文献：
  名称：

  苯并菲结构的不对称二取代酰基硫脲的合成及抗肿瘤活性

  摘要：

  一系列具有氢菲结构稠合的新颖不对称二取代acylthioureas由来自Δ合成8 -dihydroabietic和脱氢松香酸分别。它们的结构通过IR，1 H-和13 C-NMR光谱表征。通过MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物）方法评估标题化合物对SMMC7721和A549肿瘤细胞的抗肿瘤活性。结果表明，三种化合物（4C1，4D1和4D2）抗SMMC7721和A549细胞，其表现出的IC高度有效的活动50SMMC7721细胞的值分别在1.87–12.67μM和A549细胞的2.20–6.79μM之间。这表明该acylthioureas呋喃基与稠合Δ结构-活性关系8 -dihydroabietyl基，三羟甲基稠合与Δ 8 -dihydroabietyl和脱氢松香可以产生增强这种针对SMMC7721和A549细胞的化合物的活性。

  DOI：

  10.1007/s00044-010-9303-8

文献信息

• Synthesis and antitumor activities of novel α-aminophosphonates dehydroabietic acid derivatives
  作者：Xiao-Chao Huang、Meng Wang、Ying-Ming Pan、Xiao-Yan Tian、Heng-Shan Wang、Ye Zhang

  DOI：10.1016/j.bmcl.2013.08.005

  日期：2013.10

  A series of novel alpha-aminophosphonate derivatives containing DHA structure were designed and synthesized as antitumor agents. In vitro antitumor activities of these compounds against the NCI-H460 (human lung cancer cell), A549 (human lung adenocarcinoma cell), HepG2 (human liver cancer cell) and SKOV3 (human ovarian cancer cell) human cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The pharmacological screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-FU. The action mechanism of representative compound 7c was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound can induce cell apoptosis in NCI-H460 cells. Cell cycle analysis showed that compound 7c mainly arrested NCI-H460 cells in G1 stage. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and antitumor activities of unsymmetrically disubstituted acylthioureas fused with hydrophenanthrene structure
  作者：Xiao-Ping Rao、Yong Wu、Zhan-Qian Song、Shi-Bin Shang、Zong-De Wang

  DOI：10.1007/s00044-010-9303-8

  日期：2011.4

  A series of novel unsymmetrically disubstituted acylthioureas fused with hydrophenanthrene structure were synthesized from Δ8-dihydroabietic and dehydroabietic acid, respectively. Their structures were characterized by IR, 1H-, and 13C-NMR spectroscopy. The antitumor activities of the title compounds against SMMC7721 and A549 tumor cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium

  一系列具有氢菲结构稠合的新颖不对称二取代acylthioureas由来自Δ合成8 -dihydroabietic和脱氢松香酸分别。它们的结构通过IR，1 H-和13 C-NMR光谱表征。通过MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物）方法评估标题化合物对SMMC7721和A549肿瘤细胞的抗肿瘤活性。结果表明，三种化合物（4C1，4D1和4D2）抗SMMC7721和A549细胞，其表现出的IC高度有效的活动50SMMC7721细胞的值分别在1.87–12.67μM和A549细胞的2.20–6.79μM之间。这表明该acylthioureas呋喃基与稠合Δ结构-活性关系8 -dihydroabietyl基，三羟甲基稠合与Δ 8 -dihydroabietyl和脱氢松香可以产生增强这种针对SMMC7721和A549细胞的化合物的活性。
• Synthesis and pharmacological evaluation of dehydroabietic acid thiourea derivatives containing bisphosphonate moiety as an inducer of apoptosis
  作者：Xiaochao Huang、Rizheng Huang、Zhixin Liao、Yingming Pan、Shaohua Gou、Hengshan Wang

  DOI：10.1016/j.ejmech.2015.12.008

  日期：2016.1

  A series of DHAA thiourea derivatives containing bisphosphonate moiety were designed and synthesized as potent antitumor agents. Structures of target molecules were confirmed using HR-MS,H-1 NMR and C-13 NMR and they exhibited potent anti-tumor activities against the SK-OV-3, BEL-7404, A549, HCT-116 and NCI-H460 tumor cell lines in vitro. Especially, compound 6e (IC50 = 1.79 +/- 0.43 mu M) exhibited the best anticancer activity against SK-OV-3 cell line. Its role as an inducer of apoptosis was investigated in this cell line by Annexin-V/PI binding assay and by following its capability for ROS generation, depolarization of mitochondrial transmembrane potential, activation of caspases and expression of pro- and anti-apoptotic proteins. Elevated level of ROS generation, activation of caspase-3, caspase-8, caspase-9, and Fas, higher expression of Bax, lower expression of Bcl-2, and increased level of Bax/Bcl-2 ratio identified 6e as a promising inducer of apoptosis that follows both of the mitochondria dependent pathway and the death receptor-mediated pathway. In addition, the cell cycle analysis indicated that compound 6e caused cell cycle arrest at G1 phase, induced apoptosis and led to cell death by increasing the proportion of sub G1 cells. Furthermore, molecular docking studies showed that 6e could bind to the ATP pocket sites. (C) 2015 Elsevier Masson SAS. All rights reserved.