(2S,3R,4S,5S)-3-[(1S,2S)-1-(benzyloxy)-2-methylbutyl]-4-nitro-5-phenylpyrrolidine-2-carboxylic acid | 858367-06-3

• 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-[(1S,2S)-1-(benzyloxy)-2-methylbutyl]-4-nitro-5-phenylpyrrolidine-2-carboxylic acid
• 英文别名: (2S,3R,4S,5S)-3-[(1S,2S)-2-methyl-1-phenylmethoxybutyl]-4-nitro-5-phenylpyrrolidine-2-carboxylic acid
• CAS: 858367-06-3
• 化学式: C₂₃H₂₈N₂O₅
• 分子量: 412.486
• InChiKey: IBZVAATXTVWVIW-XTRYRTTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,5S)-3-[(1S,2S)-1-(benzyloxy)-2-methylbutyl]-4-nitro-5-phenylpyrrolidine-2-carboxylic acid 在 lithium hydroxide 、 氰基磷酸二乙酯 、 三乙胺 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 2-{(2S,3R,4S,5S)-3-[(1S,2S)-1-(benzyloxy)-2-methylbutyl]-4-nitro-5-phenylpyrrolidine-2-carboxamido}acetic 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 、 水 、 silver(I) acetate 、 对甲苯磺酸 、 三乙胺 、 2,2-二甲氧基丙烷 、 lithium hydroxide 、 sodium nitrite 作用下， 以 甲醇 、 乙二醇二甲醚 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 149.25h， 生成 (2S,3R,4S,5S)-3-[(1S,2S)-1-(benzyloxy)-2-methylbutyl]-4-nitro-5-phenylpyrrolidine-2-carboxylic acid
  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

• Novel synthetic compounds, processes of manufacture and uses in the treatment of integrin-mediated disorders
  申请人：Cossio Pedro Fernando

  公开号：US20060211630A1

  公开（公告）日：2006-09-21

  This invention relates to nitroproline derivative compounds and procedures for their preparation and the preparation of pharmaceutical compositions containing the compounds. The invention also relates to the administration of compounds of the invention as agents for the treatment of mammalian diseases whose pathogenic and pathophysiological mechanisms depend on or are significantly contributed by undesirable cellular and molecular activities or responses induced by integrin-dependent molecular interactions.

  本发明涉及硝基脯氨酸衍生物化合物及其制备方法以及含有该化合物的药物组合物的制备。该发明还涉及将本发明的化合物作为治疗哺乳动物疾病的药剂的用途，该疾病的病原学和病理生理学机制取决于或主要受到不良细胞和分子活动或由整合素依赖的分子相互作用引起的不良反应的贡献。
• Novel Inhibitors of the Lfa-1/Icam-1 Interaction and Uses Thereof
  申请人：Cossio Mora Fernando Pedro

  公开号：US20080249157A1

  公开（公告）日：2008-10-09

  The invention relates to the treatment of disorders or diseases mediated by LFA-1/ICAM-1 molecular interaction. This is based on the use of novel chemical compounds capable of inhibiting said interaction, and more particularly, to pharmaceutical compositions containing these compounds.

  该发明涉及通过LFA-1/ICAM-1分子相互作用介导的疾病或疾病的治疗。这是基于使用能够抑制该相互作用的新型化学化合物，更具体地说，是关于含有这些化合物的药物组合物。
• WO2007/54128
  申请人：——

  公开号：——

  公开（公告）日：——
• US7446125B2
  申请人：——

  公开号：US7446125B2

  公开（公告）日：2008-11-04
• US7943660B2
  申请人：——

  公开号：US7943660B2

  公开（公告）日：2011-05-17