N-(1-ylooxy-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl)-L-phenylalanine | 71645-10-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(1-ylooxy-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl)-L-phenylalanine
• CAS: 71645-10-8
• 化学式: C₁₉H₂₇N₂O₅
• 分子量: 363.434
• InChiKey: DBULLDCGDZJMSG-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(1-ylooxy-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl)-L-phenylalanine 在 4-二甲氨基吡啶 、 苯肼 、 N,N'-二环己基碳二亚胺 作用下， 以 氘代氯仿 、 二氯甲烷 为溶剂， 反应 2.17h， 生成 [(5R,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl] (2S)-2-[(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)oxycarbonylamino]-3-phenylpropanoate
  参考文献：
  名称：

  Synthesis of Novel Spin‐Labeled Derivatives of Podophyllotoxin as Potential Antineoplastic Agents

  摘要：

  Five novel nitroxyl spin-labeled ester derivatives of podophyllotoxin have been prepared by reacting the corresponding N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl) amino acids with the hydroxy group of podophyllotoxin in the presence of dimethylaminopyridine and N,N-dicyclohexylcarbodiimide and evaluated as potential antitumor agents. All of the target compounds showed more significant cytotoxicity against P-388 murine leukemia and A-549 human lung carcinoma in vitro than etoposide.

  DOI：

  10.1080/00397910500287983
• 作为产物：
  描述：

  阻聚剂701 在 magnesium oxide 、 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 N-(1-ylooxy-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl)-L-phenylalanine
  参考文献：
  名称：

  新型5-FU的自旋标记衍生物的合成作为潜在的抗肿瘤药。

  摘要：

  化学疗法是各种癌症（包括肺癌）的一般治疗选择。为了找到对肺癌具有较高生物活性和较低毒性的化合物，合成了新型自旋标记的5-氟尿嘧啶（5-FU）衍生物（3a - f），并针对四种人类肿瘤细胞系（A-549，DU- 145，KB和KBvin）。两种有希望的化合物3d和3f对非小细胞肺癌细胞A-549的IC 50值分别为2.76和2.38μM。这些化合物的细胞毒性是5-FU的两倍，对其他测试细胞系的毒性也较小。化合物3f对A-549的选择性细胞毒性是5-FU的7倍。我们的结果表明，化合物3d和3f值得进一步研究，以发展成为非小细胞肺癌的临床试验候选药物。

  DOI：

  10.1007/s00044-013-0906-8

文献信息

• Synthesis and mechanistic studies of novel spin-labeled combretastatin derivatives as potential antineoplastic agents
  作者：Ying-Qian Liu、Xiao-Jing Li、Chun-Yan Zhao、Xiang Nan、Jing Tian、Susan L. Morris-Natschke、Zhi-Jun Zhang、Xiao-Ming Yang、Liu Yang、Lin-Hai Li、Xing-Wen Zhou、Kuo-Hsiung Lee

  DOI：10.1016/j.bmc.2012.12.046

  日期：2013.3

  Two series (14a–d and 21a–h) of novel spin-labeled combretastatin derivatives were synthesized and evaluated for cytotoxicity against four tumor cell lines (K562, SGC-7901, Hela and HepG-2). Simultaneously, a representative compound 21a was selected to investigate the antitumor mechanisms of these synthetic compounds. The results indicated that some of the compounds showed significant cytotoxicity

  合成了两个系列（14a – d和21a – h）的新型自旋标记的康他汀衍生物，并评估了它们对四种肿瘤细胞系（K562，SGC-7901，Hela和HepG-2）的细胞毒性。同时，选择代表性的化合物21a来研究这些合成化合物的抗肿瘤机理。结果表明，某些化合物在体外对四种肿瘤细胞系表现出显着的细胞毒性，并且比临床可用的抗癌药物依托泊苷具有更高的活性。在新合成的化合物中，21a，21b和21c对三种测试的肿瘤细胞系（HEPG-2，BGC-832和Hela）显示出最大的细胞毒性，IC 50值范围为0.15至1.05μM，3-氨基-脱氧Combretastatin A-4的值为0.014-0.403μM （3）。另外，机理分析表明，化合物21a有效地干扰微管蛋白动力学以防止癌细胞中的有丝分裂，从而导致细胞周期停滞并最终导致剂量依赖性细胞凋亡。
• Design, synthesis and cytotoxic activity of novel spin-labeled rotenone derivatives
  作者：Ying-Qian Liu、Emika Ohkoshi、Lin-Hai Li、Liu Yang、Kuo-Hsiung Lee

  DOI：10.1016/j.bmcl.2011.12.024

  日期：2012.1

  Three series of novel spin-labeled rotenone derivatives were synthesized and evaluated for cytotoxicity against four tumor cell lines, A-549, DU-145, KB and KBvin. All of the derivatives showed promising in vitro cytotoxic activity against the tumor cell lines tested, with IC50 values ranging from 0.075 to 0.738 μg/mL. Remarkably, all of the compounds were more potent than paclitaxel against KBvin

  合成了三个系列的新型自旋标记鱼藤酮衍生物，并评估了它们对四种肿瘤细胞系A-549，DU-145，KB和KBvin的细胞毒性。所有衍生物均显示出对测试的肿瘤细胞系有希望的体外细胞毒性活性，IC 50值范围为0.075至0.738μg/ mL。值得注意的是，所有化合物在体外对KBvin的作用均优于紫杉醇，并且化合物3a和3d对这种细胞系表现出最高的细胞毒性（IC 50分别为0.075和0.092μg/ mL）。基于观察到的细胞毒性，已经描述了结构-活性关系。
• First synthesis and biological evaluation of novel spin-labeled derivatives of deoxypodophyllotoxin
  作者：Zhi-Wei Zhang、Jia-Qiang Zhang、Ling Hui、Shi-Wu Chen、Xuan Tian

  DOI：10.1016/j.ejmech.2009.12.032

  日期：2010.4

  Deoxypodophyllotoxin inhibits tubulin polymerization and induces cell cycle arrest at G2/M, followed by apoptosis. In order to find compounds with superior bioactivity and less toxicity, a series of spin-labeled derivatives of deoxypodophyllotoxin were synthesized by reacting 4'-demethyl-4-deoxypodophyllotoxin (DPPT) with N-(1-oxy1-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl) amino acids. The cytotoxic activities against three tumor cell lines (HL-60, RPMI-8226, A-549) in vitro and the antioxidative activities in tissues of Sprague Dawley (SD) rats of target compounds were evaluated, and the results indicated that compounds 11a-h were more potent in terms of cytotoxicities and antioxidative activities than either parent compound DPPT or anticancer drug VP-16. (C) 2009 Elsevier Masson SAS. All rights reserved.
• Novel semisynthetic spin-labeled derivatives of podophyllotoxin with cytotoxic and antioxidative activity
  作者：Jia-Qiang Zhang、Zhi-Wei Zhang、Ling Hui、Shi-Wu Chen、Xuan Tian

  DOI：10.1016/j.bmcl.2009.12.048

  日期：2010.2

  A series of novel spin-labeled podophyllotoxin derivatives were synthesized by reacting the corresponding N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxy carbonyl)-amino acids with 4 beta-amino-4'-demethylepipodophyllotoxin. The synthesized derivatives 12a-g were evaluated for the partition coefficients, cytotoxicities in vitro against three tumor cell lines (A-549, HL-60, and RPMI-8226) and antioxidative activities in tissues of SD rats by the TBA method. The vast majority of target compounds have shown superior or comparable activities against A-549, HL-60, and RPMI-8226 compared to VP-16, and they have shown more significant antioxidative activities and superior water solubility than VP-16. (c) 2009 Elsevier Ltd. All rights reserved.
• Synthesis of novel spin-labeled derivatives of 5-FU as potential antineoplastic agents
  作者：Liu Yang、Mei-Juan Wang、Zhi-Jun Zhang、Susan L. Morris-Natschke、Masuo Goto、Jing Tian、Ying-Qian Liu、Chih-Ya Wang、Xuan Tian、Xiao-Ming Yang、Kuo-Hsiung Lee

  DOI：10.1007/s00044-013-0906-8

  日期：2014.7

  treatment option for various cancers, including lung cancer. In order to find compounds with superior bioactivity and less toxicity against lung cancer, novel spin-labeled 5-fluorouracil (5-FU) derivatives (3a–f) were synthesized and evaluated against four human tumor cell lines (A-549, DU-145, KB, and KBvin). Two promising compounds 3d and 3f exhibited IC50 values of 2.76 and 2.38 μM, respectively

  化学疗法是各种癌症（包括肺癌）的一般治疗选择。为了找到对肺癌具有较高生物活性和较低毒性的化合物，合成了新型自旋标记的5-氟尿嘧啶（5-FU）衍生物（3a - f），并针对四种人类肿瘤细胞系（A-549，DU- 145，KB和KBvin）。两种有希望的化合物3d和3f对非小细胞肺癌细胞A-549的IC 50值分别为2.76和2.38μM。这些化合物的细胞毒性是5-FU的两倍，对其他测试细胞系的毒性也较小。化合物3f对A-549的选择性细胞毒性是5-FU的7倍。我们的结果表明，化合物3d和3f值得进一步研究，以发展成为非小细胞肺癌的临床试验候选药物。