(2S,4S)-4-(4-phenylphenoxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid

• 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: (2S,4S)-4-(4-phenylphenoxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid
• 英文别名: (2S,4S)-4-([1,1'-biphenyl]-4-yloxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid；(2S,4S)-4-([1,1'-Biphenyl]-4-yloxy)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid；(2S,4S)-1-[(2-methylpropan-2-yl)oxycarbonyl]-4-(4-phenylphenoxy)pyrrolidine-2-carboxylic acid
• 化学式: C₂₂H₂₅NO₅
• 分子量: 383.444
• InChiKey: RNJAAPCHTADLSB-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,4S)-4-(4-phenylphenoxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid 在 N-甲基吗啉 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 (2S,4S)-tert-butyl 4-(4-phenylphenoxy)-2-(((S)-1-(4-methylphenylsulfonamido)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis and preliminary biological studies of pyrrolidine derivatives as Mcl-1 inhibitors

  摘要：

  Anti-apoptotic proteins, such as B-cell lymphoma (Bcl-2) protein, myeloid cell leukemia sequence 1 (Mcl-1) protein, are potential targets for cancer treatment. In the studies, a series of pyrrolidine derivatives were developed as potent Mcl-1 inhibitors. The preliminary biological studies suggested that most of target compounds exhibit good abilities for targeting Mcl-1 protein. Among them, compound 21 (K-i = 0.53 mu M) exhibited equal inhibitory activities towards Mcl-1 protein compared to positive control gossypol (K-i = 0.39 mu M). This compound also possessed good antiproliferative activities against MDA-MB-231 and PC-3 cancer cells. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.014
• 作为产物：
  描述：

  反式-4-羟基-L-脯氨酸甲酯 在 potassium carbonate 、 三乙胺 、 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 1.5h， 生成 (2S,4S)-4-(4-phenylphenoxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  通过修饰氨基酸侧链提高吡咯烷衍生物作为Mcl-1抑制剂的结合亲和力。

  摘要：

  作为抗凋亡Bcl-2蛋白的重要成员，髓样细胞白血病序列1（Mcl-1）蛋白是癌症治疗的诱人靶标。在这项研究中，主要通过修饰化合物1的氨基酸侧链，开发了一系列新的吡咯烷衍生物作为Mcl-1抑制剂。其中，化合物18（Ki =0.077μM）对Mcl-1蛋白表现出更好的抑制活性。与阳性对照棉酚相比（Ki =0.18μM）。此外，化合物40对PC-3细胞具有良好的抗增殖活性（Ki =8.45μM），与阳性对照棉酚（Ki =7.54μM）相同。

  DOI：

  10.1016/j.bmc.2016.10.020

文献信息

• Design, synthesis and preliminary biological studies of pyrrolidine derivatives as Mcl-1 inhibitors
  作者：Yichao Wan、Junhua Wang、Feng’e Sun、Minglu Chen、Xuben Hou、Hao Fang

  DOI：10.1016/j.bmc.2015.11.014

  日期：2015.12

  Anti-apoptotic proteins, such as B-cell lymphoma (Bcl-2) protein, myeloid cell leukemia sequence 1 (Mcl-1) protein, are potential targets for cancer treatment. In the studies, a series of pyrrolidine derivatives were developed as potent Mcl-1 inhibitors. The preliminary biological studies suggested that most of target compounds exhibit good abilities for targeting Mcl-1 protein. Among them, compound 21 (K-i = 0.53 mu M) exhibited equal inhibitory activities towards Mcl-1 protein compared to positive control gossypol (K-i = 0.39 mu M). This compound also possessed good antiproliferative activities against MDA-MB-231 and PC-3 cancer cells. (c) 2015 Elsevier Ltd. All rights reserved.
• Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains
  作者：Yichao Wan、Tingting Liu、Xiaoxian Li、Chen Chen、Hao Fang

  DOI：10.1016/j.bmc.2016.10.020

  日期：2017.1

  member of anti-apoptotic Bcl-2 protein, myeloid cell leukemia sequence 1 (Mcl-1) protein is an attractive target for cancer therapy. In this study, a new series of pyrrolidine derivatives as Mcl-1 inhibitors were developed by mainly modifying the amino acid side chain of compound 1. Among them, compound 18 (Ki=0.077μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive

  作为抗凋亡Bcl-2蛋白的重要成员，髓样细胞白血病序列1（Mcl-1）蛋白是癌症治疗的诱人靶标。在这项研究中，主要通过修饰化合物1的氨基酸侧链，开发了一系列新的吡咯烷衍生物作为Mcl-1抑制剂。其中，化合物18（Ki =0.077μM）对Mcl-1蛋白表现出更好的抑制活性。与阳性对照棉酚相比（Ki =0.18μM）。此外，化合物40对PC-3细胞具有良好的抗增殖活性（Ki =8.45μM），与阳性对照棉酚（Ki =7.54μM）相同。