(2S)-1-(2-oxo-2-phenylacetyl)-N-(3-phenylpropyl)piperidine-2-carboxamide | 1421280-18-3

• 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)-1-(2-oxo-2-phenylacetyl)-N-(3-phenylpropyl)piperidine-2-carboxamide
• 英文别名: tert-butyl (S)-2-((3-phenylpropyl)carbamoyl)piperidine-1-carboxylate；tert-butyl (2S)-2-(3-phenylpropylcarbamoyl)piperidine-1-carboxylate
• CAS: 1421280-18-3
• 化学式: C₂₀H₃₀N₂O₃
• 分子量: 346.47
• InChiKey: QGIDARUIWVGTKD-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S)-1-(2-oxo-2-phenylacetyl)-N-(3-phenylpropyl)piperidine-2-carboxamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以72%的产率得到(2S)-1-(2-oxo-2-phenylacetyl)-N-(3-phenylpropyl)piperidine-2-carboxamide
  参考文献：
  名称：

  The Precise Chemical–Physical Nature of the Pharmacore in FK506 Binding Protein Inhibition: ElteX, a New Class of Nanomolar FKBP12 Ligands

  摘要：

  Due to its central role in immunosuppression and cell proliferation and due to its specific peptidyl-prolyl-isomerase (PPI) function, the FKBP protein family is at the crossroad of several important metabolic pathways. Members of this family, and notably R(506 binding protein (FKBP12), are thought to be involved in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, as well as in proliferation disorders and cancer. Using an interdisciplinary approach based on computational, synthetic, and experimental techniques, we show that the best potential binders for FKBP proteins optimally expose the two contiguous carbonyl oxygen in the proline-mimetic chain for FKBP docking and are characterized by the abundance of rigid quasi-cyclic structures stabilized in aqueous solution by intraligand hydrophobic interactions mimicking the macrolide structure of the natural FKBP binders FK506 and Rapamycin. These peculiar structural and chemical-physical features define at the same time an ElteX compound and the minimal pharmacore in the FKBP family, shedding new light on the isomerization mechanism of the PPI domain. On the basis of the above hypothesis, we have successfully designed and synthesized several nanomolar ElteX FKBP12 ligands. Among these, ElteN378 is a new low atomic weight ligand with affinity comparable to that of the macrolide Rapamycin.

  DOI：

  10.1021/jm3015052
• 作为产物：
  描述：

  3-苯基-1-丙胺 、 N-Boc-L-哌啶-2-羧酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以80%的产率得到(2S)-1-(2-oxo-2-phenylacetyl)-N-(3-phenylpropyl)piperidine-2-carboxamide
  参考文献：
  名称：

  [EN] A COMPOUND FOR THE DETERMINATION OF THE PROTEIN FKBP12 AND A SENSOR UNIT COMPRISING IT
  [FR] COMPOSÉ POUR LA DÉTERMINATION DE LA PROTÉINE FKBP12 ET UNITÉ DE CAPTEUR COMPRENANT CELUI-CI

  摘要：

  本发明涉及一种新型化合物，可用作传感器，用于快速和特异地确定FKBP12蛋白质，一种肽基脯氨酸顺反异构酶（PPlase），如果受试者的生物体液中的FKBP12蛋白质水平发生变化，那么受试者受到病理条件的影响，特别是神经退行性疾病，如帕金森病和阿尔茨海默氏综合征，肿瘤病理学，自身免疫疾病，或者受试者在器官移植后处于急性排斥阶段。

  公开号：

  WO2021124269A1

文献信息

• [EN] A COMPOUND FOR THE DETERMINATION OF THE PROTEIN FKBP12 AND A SENSOR UNIT COMPRISING IT<br/>[FR] COMPOSÉ POUR LA DÉTERMINATION DE LA PROTÉINE FKBP12 ET UNITÉ DE CAPTEUR COMPRENANT CELUI-CI
  申请人：UNIV DEGLI STUDI DI FIRENZE

  公开号：WO2021124269A1

  公开（公告）日：2021-06-24

  The present invention relates to novel compounds useful as sensors for the rapid and specific determination of the FKBP12 protein, a peptidyl-prolyl cis-trans isomerase (PPlase), the levels of which in the biological fluids of a subject change if the subject is affected by pathological conditions, in particular neurodegenerative diseases, such as the Parkinson's disease and the Alzheimer's syndrome, tumour pathologies, autoimmune diseases, or if that subject is in a phase of acute rejection after organ transplantation.

  本发明涉及一种新型化合物，可用作传感器，用于快速和特异地确定FKBP12蛋白质，一种肽基脯氨酸顺反异构酶（PPlase），如果受试者的生物体液中的FKBP12蛋白质水平发生变化，那么受试者受到病理条件的影响，特别是神经退行性疾病，如帕金森病和阿尔茨海默氏综合征，肿瘤病理学，自身免疫疾病，或者受试者在器官移植后处于急性排斥阶段。
• The Precise Chemical–Physical Nature of the Pharmacore in FK506 Binding Protein Inhibition: ElteX, a New Class of Nanomolar FKBP12 Ligands
  作者：Maria Raffaella Martina、Eleonora Tenori、Marco Bizzarri、Stefano Menichetti、Gabriella Caminati、Piero Procacci

  DOI：10.1021/jm3015052

  日期：2013.2.14

  Due to its central role in immunosuppression and cell proliferation and due to its specific peptidyl-prolyl-isomerase (PPI) function, the FKBP protein family is at the crossroad of several important metabolic pathways. Members of this family, and notably R(506 binding protein (FKBP12), are thought to be involved in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, as well as in proliferation disorders and cancer. Using an interdisciplinary approach based on computational, synthetic, and experimental techniques, we show that the best potential binders for FKBP proteins optimally expose the two contiguous carbonyl oxygen in the proline-mimetic chain for FKBP docking and are characterized by the abundance of rigid quasi-cyclic structures stabilized in aqueous solution by intraligand hydrophobic interactions mimicking the macrolide structure of the natural FKBP binders FK506 and Rapamycin. These peculiar structural and chemical-physical features define at the same time an ElteX compound and the minimal pharmacore in the FKBP family, shedding new light on the isomerization mechanism of the PPI domain. On the basis of the above hypothesis, we have successfully designed and synthesized several nanomolar ElteX FKBP12 ligands. Among these, ElteN378 is a new low atomic weight ligand with affinity comparable to that of the macrolide Rapamycin.