(S)-tert-butyl 1-(4-fluorophenyl)-2-hydroxyethylcarbamate | 1139818-79-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-tert-butyl 1-(4-fluorophenyl)-2-hydroxyethylcarbamate
• 英文别名: tert-Butyl (S)-(1-(4-fluorophenyl)-2-hydroxyethyl)carbamate；tert-butyl N-[(1S)-1-(4-fluorophenyl)-2-hydroxyethyl]carbamate
• CAS: 1139818-79-3
• 化学式: C₁₃H₁₈FNO₃
• 分子量: 255.289
• InChiKey: XQJURJIJCWFLRP-LLVKDONJSA-N

物化性质

• 沸点：
  383.8±37.0 °C(Predicted)
• 密度：
  1.162±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 1-(4-fluorophenyl)-2-hydroxyethylcarbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 (2S)-2-氨基-2-(4-氟苯基)乙醇
  参考文献：
  名称：

  Significance of interactions of BACE1–Arg235 with its ligands and design of BACE1 inhibitors with P2 pyridine scaffold

  摘要：

  Recently, we reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Because these inhibitors contained some natural amino acids, we would need to improve their enzymatic stability in vivo and permeability across the blood-brain barrier, so that they become practically useful. Subsequently, non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold, 2,6-pyridenedicarboxylic, chelidamic or chelidonic moiety, at the P-2 position were reported. These inhibitors were designed based on the conformer of docked inhibitor in BACE1. In this study, we discuss the role and significance of interactions between Arg235 of BACE1 and its inhibitor in BACE1 inhibitory mechanism. Moreover, we designed more potent small-sized BACE1 inhibitors with a 2,6-pyridinedicarboxylic scaffold at the P2 position, that were optimized for the interactions with Arg235 of BACE1. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.049
• 作为产物：
  描述：

  N-boc-4'-fluoro-(S)-phenylglycine methyl ester 在 锂硼氢 作用下， 以 甲醇 为溶剂， 生成 (S)-tert-butyl 1-(4-fluorophenyl)-2-hydroxyethylcarbamate
  参考文献：
  名称：

  Significance of interactions of BACE1–Arg235 with its ligands and design of BACE1 inhibitors with P2 pyridine scaffold

  摘要：

  Recently, we reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Because these inhibitors contained some natural amino acids, we would need to improve their enzymatic stability in vivo and permeability across the blood-brain barrier, so that they become practically useful. Subsequently, non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold, 2,6-pyridenedicarboxylic, chelidamic or chelidonic moiety, at the P-2 position were reported. These inhibitors were designed based on the conformer of docked inhibitor in BACE1. In this study, we discuss the role and significance of interactions between Arg235 of BACE1 and its inhibitor in BACE1 inhibitory mechanism. Moreover, we designed more potent small-sized BACE1 inhibitors with a 2,6-pyridinedicarboxylic scaffold at the P2 position, that were optimized for the interactions with Arg235 of BACE1. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.049

文献信息

• [EN] GAMMA SECRETASE MODULATORS<br/>[FR] MODULATEURS DE GAMMA SECRÉTASE
  申请人：SCHERING CORP

  公开号：WO2009045314A1

  公开（公告）日：2009-04-09

  In its many embodiments, the present invention provides a novel class of 5-membered, nitrogen-containing heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

  在其许多实施例中，本发明提供了一种新型的含氮杂环5-成员化合物，作为γ-分泌酶的调节剂，制备这种化合物的方法，含有一种或多种这种化合物的药物组合物，制备包含一种或多种这种化合物的药物配方的方法，以及使用这种化合物或药物组合物治疗、预防、抑制或改善与中枢神经系统相关的一种或多种疾病的方法。
• Discovery and Optimization of Phosphopantetheine Adenylyltransferase Inhibitors with Gram-Negative Antibacterial Activity
  作者：Colin K. Skepper、Robert J. Moreau、Brent A. Appleton、Bret M. Benton、Joseph E. Drumm、Brian Y. Feng、Mei Geng、Cheng Hu、Cindy Li、Andreas Lingel、Yipin Lu、Mulugeta Mamo、Wosenu Mergo、Mina Mostafavi、Christopher M. Rath、Micah Steffek、Kenneth T. Takeoka、Kyoko Uehara、Lisha Wang、Jun-Rong Wei、Lili Xie、Wenjian Xu、Qiong Zhang、Javier de Vicente

  DOI：10.1021/acs.jmedchem.7b01861

  日期：2018.4.26

  adenylyltransferase inhibitors (PPAT, CoaD). Following several rounds of optimization two promising lead compounds were identified: triazolopyrimidinone 3 and 4-azabenzimidazole 4. Here we disclose our efforts to further optimize these two leads for on-target potency and Gram-negative cellular activity. Enabled by a robust X-ray crystallography system, our structure-based inhibitor design approach delivered

  在前面的手稿中[Moreau et al。2018，10.1021 / acs.jmedchem.7b01691]我们描述了一个成功的基于片段的铅发现（FBLD）策略用于细菌磷酸泛酰腺苷酰转移酶抑制剂（PPAT，COAD）的发现。经过几轮优化，确定了两个有前途的先导化合物：三唑并嘧啶酮3和4-氮杂苯并咪唑4。在这里，我们公开了我们的工作，以进一步优化针对靶点效力和革兰氏阴性细胞活性的这两种线索。借助强大的X射线晶体学系统，我们基于结构的抑制剂设计方法可提供具有比其各自片段起始点大4–5个数量级的生化潜能的化合物。通过对细菌渗透性和理化性质的观察指导其他优化，这最终导致鉴定出具有针对野生型大肠杆菌的细胞活性的PPAT抑制剂。
• GAMMA SECRETASE MODULATORS
  申请人：Zhu Zhaoning

  公开号：US20100298381A1

  公开（公告）日：2010-11-25

  In its many embodiments, the present invention provides a novel class of 5-membered, nitrogen-containing heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

  在其多种实施方式中，本发明提供了一种新型的5-成员、含氮杂环化合物作为γ-分泌酶调节剂，制备这种化合物的方法，含有一种或多种这种化合物的制药组合物，制备包含一种或多种这种化合物的制药制剂的方法，以及使用这种化合物或制药组合物治疗、预防、抑制或改善与中枢神经系统相关的一种或多种疾病的方法。
• Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered Cancers
  作者：Lizbeth DeSelm、Bayard Huck、Ruoxi Lan、Constantin Neagu、Justin Potnick、Yufang Xiao、Xiaoling Chen、Reinaldo Jones、Thomas E. Richardson、Brian H. Heasley、Thomas Haxell、Joseph Moore、Hui Tian、Katrin Georgi、Felix Rohdich、Amanda Sutton、Theresa Johnson、Igor Mochalkin、Jennifer Jackson、Jing Lin、Lindsey Crowley、Andreas Machl、Anderson Clark、Erik Wilker、Brian Sherer、Andreas Goutopoulos

  DOI：10.1021/acs.jmedchem.1c01087

  日期：2021.10.14
• Significance of interactions of BACE1–Arg235 with its ligands and design of BACE1 inhibitors with P2 pyridine scaffold
  作者：Yoshio Hamada、Hiroko Ohta、Naoko Miyamoto、Diganta Sarma、Takashi Hamada、Tomoya Nakanishi、Moe Yamasaki、Abdellah Yamani、Shoichi Ishiura、Yoshiaki Kiso

  DOI：10.1016/j.bmcl.2009.03.049

  日期：2009.5

  Recently, we reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Because these inhibitors contained some natural amino acids, we would need to improve their enzymatic stability in vivo and permeability across the blood-brain barrier, so that they become practically useful. Subsequently, non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold, 2,6-pyridenedicarboxylic, chelidamic or chelidonic moiety, at the P-2 position were reported. These inhibitors were designed based on the conformer of docked inhibitor in BACE1. In this study, we discuss the role and significance of interactions between Arg235 of BACE1 and its inhibitor in BACE1 inhibitory mechanism. Moreover, we designed more potent small-sized BACE1 inhibitors with a 2,6-pyridinedicarboxylic scaffold at the P2 position, that were optimized for the interactions with Arg235 of BACE1. (c) 2009 Elsevier Ltd. All rights reserved.