(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid
• 英文别名: (2S)-2-(1-tert-butoxycarbonyl-4-piperidyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)acetic acid；Fmoc-1(1-boc-piperidin-4-YL)-DL-glycine；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]acetic acid
• 化学式: C₂₇H₃₂N₂O₆
• 分子量: 480.561
• InChiKey: ATJZZVCJRHLAGA-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid 在 三甲基硅烷化重氮甲烷 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、310.27 kPa 条件下， 生成 4-((S)-Amino-methoxycarbonyl-methyl)-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Potent and Selective Carboxylic Acid-Based Inhibitors of Matrix Metalloproteinases

  摘要：

  A novel series of carboxylic acids containing a substituted piperidine were synthesized and tested for inhibition of selected matrix metalloproteinases. Multiple analogues prepared based on this novel design were found to inhibit the target MMPs (MMP-2, -3, -8, -9, and -13) with unprecedented, low nanomolar potency while, at the same time, sparing MMP-1 and MMP-7. Solubility and plasma protein binding of several members of this new series of carboxylic acids were also investigated.

  DOI：

  10.1021/jm015531s
• 作为产物：
  描述：

  (S)-1-boc-4-(氨基羧基甲基)哌啶 、 氯甲酸-9-芴基甲酯 在 sodium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 以98%的产率得到(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid
  参考文献：
  名称：

  [EN] CONJUGATES COMPRISING RIPK2 INHIBITORS
  [FR] CONJUGUÉS COMPRENANT DES INHIBITEURS DE RIPK2

  摘要：

  本发明涉及化合物、组合物、组合物和含有所述化合物的药物以及其制备方法。该发明还涉及所述化合物、组合物、组合物和药物的用途，例如作为RIP2激酶活性的抑制剂，包括降解RIP2激酶，用于治疗由RIP2激酶介导的疾病和症状，特别是用于治疗炎症性疾病或症状。

  公开号：

  WO2017182418A1

文献信息

• [EN] CONJUGATES COMPRISING RIPK2 INHIBITORS<br/>[FR] CONJUGUÉS COMPRENANT DES INHIBITEURS DE RIPK2
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017182418A1

  公开（公告）日：2017-10-26

  The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.

  本发明涉及化合物、组合物、组合物和含有所述化合物的药物以及其制备方法。该发明还涉及所述化合物、组合物、组合物和药物的用途，例如作为RIP2激酶活性的抑制剂，包括降解RIP2激酶，用于治疗由RIP2激酶介导的疾病和症状，特别是用于治疗炎症性疾病或症状。
• High-Affinity Peptidomimetic Inhibitors of the DCN1-UBC12 Protein–Protein Interaction
  作者：Haibin Zhou、Weihua Zhou、Bing Zhou、Liu Liu、Ting-Rong Chern、Krishnapriya Chinnaswamy、Jianfeng Lu、Denzil Bernard、Chao-Yie Yang、Shasha Li、Mi Wang、Jeanne Stuckey、Yi Sun、Shaomeng Wang

  DOI：10.1021/acs.jmedchem.7b01455

  日期：2018.3.8

  evaluation of peptidomimetics targeting the DCN1-UBC12 protein–protein interaction. Starting from a 12-residue UBC12 peptide, we have successfully obtained a series of peptidomimetic compounds that bind to DCN1 protein with KD values of <10 nM. Determination of a cocrystal structure of a potent peptidomimetic inhibitor complexed with DCN1 provides the structural basis for their high-affinity interaction

  Cullin-ring连接酶（CRL）调节哺乳动物细胞中蛋白质约20％的周转率，是人类疾病中新兴的治疗靶标。CRL的激活需要其cullin亚基的酯化，这由Cullin-RBX1-UBC12-NEDD8-DCN1组成的激活复合物控制。在本文中，我们描述了针对DCN1-UBC12蛋白与蛋白相互作用的拟肽模拟物的设计，合成和评估。从12个残基的UBC12肽开始，我们成功地获得了一系列与K D结合DCN1蛋白的拟肽化合物值<10 nM。与DCN1络合的有效拟肽抑制剂共晶体结构的确定为其高亲和力相互作用提供了结构基础。对一种有效的DCN1抑制剂化合物36（DI-404）进行的细胞研究显示，与其他cullin成员相比，它有效且选择性地抑制cullin 3的二烯化。DI-404的进一步优化可能会产生一类用于治疗人类疾病的新型疗法，其中cullin 3 CRL起着关键作用。
• Conjugates comprising RIPK2 inhibitors
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US10781205B2

  公开（公告）日：2020-09-22

  The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.

  本发明涉及含有所述化合物的化合物、组合物、组合物和药物及其制备工艺。 本发明还涉及所述化合物、组合物、组合物和药物的用途，例如作为 RIP2 激酶活性的抑制剂，包括降解 RIP2 激酶，治疗由 RIP2 激酶介导的疾病和病症，特别是治疗炎症性疾病或病症。
• Substituted piperidinyl glycinyl 2-cyano-4,5-methano pyrrolidines as potent and stable dipeptidyl peptidase IV inhibitors
  作者：Guohua Zhao、Chet Kwon、Aiying Wang、James G. Robertson、Jovita Marcinkeviciene、Rex A. Parker、Mark S. Kirby、Lawrence G. Hamann

  DOI：10.1016/j.bmcl.2013.01.104

  日期：2013.3

  Synthesis and structure-activity relationship of a series of substituted piperidinyl glycine 2-cyano-4,5-methano pyrroline DPP-IV inhibitors are described. Improvement of the inhibitory activity and chemical stability of this series of compounds was respectively achieved by the introduction of bulky groups at the 4-position and 1-position of the piperidinyl glycine, leading to a series of potent and stable DPP-IV inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.
• CONJUGATES COMPRISING RIPK2 INHIBITORS
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US20190119271A1

  公开（公告）日：2019-04-25

  The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.