(2S,3R,4S,5S)-3-[(S)-1-(benzyloxy)-2-methybutyl]-2-methoxycarbonyl-2-methyl-4-nitro-5-phenylpyrrolidine | 858367-23-4

• 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,3R,4S,5S)-3-[(S)-1-(benzyloxy)-2-methybutyl]-2-methoxycarbonyl-2-methyl-4-nitro-5-phenylpyrrolidine
• 英文别名: methyl (2S,3S,4S,5S)-2-methyl-3-[(1S,2S)-2-methyl-1-phenylmethoxybutyl]-4-nitro-5-phenylpyrrolidine-2-carboxylate
• CAS: 858367-23-4
• 化学式: C₂₅H₃₂N₂O₅
• 分子量: 440.539
• InChiKey: WFWRRPONRLRLCE-XRXOKJSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,5S)-3-[(S)-1-(benzyloxy)-2-methybutyl]-2-methoxycarbonyl-2-methyl-4-nitro-5-phenylpyrrolidine 在 lithium hydroxide 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 生成 (2S,3R,4S,5S)-3-[(1S,2S)-1-(benzyloxy)-2-methylbutyl]-2-methyl-4-nitro-5-phenylpyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  立体控制的逐步[3 + 2]环加成法在制备α4beta1整合素介导的肝黑色素瘤转移抑制剂中的应用。

  摘要：

  DOI：

  10.1002/anie.200462497
• 作为产物：
  描述：

  L-异亮氨酸 在 lithium aluminium tetrahydride 、 2,2,6,6-四甲基哌啶氧化物 、 硫酸 、 silver(I) acetate 、 对甲苯磺酸 、 三乙胺 、 2,2-二甲氧基丙烷 、 sodium nitrite 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 146.25h， 生成 (2S,3R,4S,5S)-3-[(S)-1-(benzyloxy)-2-methybutyl]-2-methoxycarbonyl-2-methyl-4-nitro-5-phenylpyrrolidine
  参考文献：
  名称：

  Design, Synthesis, and Functional Evaluation of Leukocyte Function Associated Antigen-1 Antagonists in Early and Late Stages of Cancer Development

  摘要：

  The integrin leukocyte function associated antigen 1 (LFA-1) binds the intercellular adhesion molecule 1 (ICAM-1) by its alpha(L)-chain inserted domain (I-domain). This interaction plays a key role in cancer and other diseases. We report the structure-based design, small-scale synthesis, and biological activity evaluation of a novel family of LFA-1 antagonists. The design led to the synthesis of a family of highly substituted homochiral pyrrolidines with antiproliferative and antimetastatic activity in a murine model of colon carcinoma, as well as potent antiadhesive properties in several cancer cell lines in the low micromolar range. NMR analysis of their binding to the isolated I-domain shows that they bind to the I-domain allosteric site (IDAS), the binding site of other allosteric LFA-1 inhibitors. These results provide evidence of the potential therapeutic value of a new set of LFA-1 inhibitors, whose further development is facilitated by a synthetic strategy that is versatile and fully stereocontrolled.

  DOI：

  10.1021/jm3016848

文献信息

• Application of Stereocontrolled Stepwise [3+2] Cycloadditions to the Preparation of Inhibitors of α4β1-Integrin-Mediated Hepatic Melanoma Metastasis
  作者：Aizpea Zubia、Lorea Mendoza、Silvia Vivanco、Eneko Aldaba、Teresa Carrascal、Begoña Lecea、Ana Arrieta、Tahl Zimmerman、Fernando Vidal-Vanaclocha、Fernando P. Cossío

  DOI：10.1002/anie.200462497

  日期：2005.5.6
• Design, Synthesis, and Functional Evaluation of Leukocyte Function Associated Antigen-1 Antagonists in Early and Late Stages of Cancer Development
  作者：Eider San Sebastián、Tahl Zimmerman、Aizpea Zubia、Yosu Vara、Elyette Martin、Finton Sirockin、Annick Dejaegere、Roland H. Stote、Xabier Lopez、David Pantoja-Uceda、María Valcárcel、Lorea Mendoza、Fernando Vidal-Vanaclocha、Fernando P. Cossío、Francisco J. Blanco

  DOI：10.1021/jm3016848

  日期：2013.2.14

  The integrin leukocyte function associated antigen 1 (LFA-1) binds the intercellular adhesion molecule 1 (ICAM-1) by its alpha(L)-chain inserted domain (I-domain). This interaction plays a key role in cancer and other diseases. We report the structure-based design, small-scale synthesis, and biological activity evaluation of a novel family of LFA-1 antagonists. The design led to the synthesis of a family of highly substituted homochiral pyrrolidines with antiproliferative and antimetastatic activity in a murine model of colon carcinoma, as well as potent antiadhesive properties in several cancer cell lines in the low micromolar range. NMR analysis of their binding to the isolated I-domain shows that they bind to the I-domain allosteric site (IDAS), the binding site of other allosteric LFA-1 inhibitors. These results provide evidence of the potential therapeutic value of a new set of LFA-1 inhibitors, whose further development is facilitated by a synthetic strategy that is versatile and fully stereocontrolled.