tert-butyl 4-(4-hydroxyanilino)piperidine-1-carboxylate | 851702-96-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(4-hydroxyanilino)piperidine-1-carboxylate
• CAS: 851702-96-0
• 化学式: C₁₆H₂₄N₂O₃
• 分子量: 292.378
• InChiKey: WERBFQRQSARVJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-hydroxyanilino)piperidine-1-carboxylate 在 4-二甲氨基吡啶 、 platinum(IV) oxide 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 20.0~80.0 ℃ 、101.33 kPa 条件下， 生成 tert-butyl 4-[4-[(2-aminophenyl)-methoxy]-N-tert-butoxycarbonyl-anilino]piperidine-1-carboxylate
  参考文献：
  名称：

  Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 2: Structure-Based Drug Design and Structure–Activity Relationship

  摘要：

  The balance of methylation levels at histone H3 lysine 4 (H3K4) is regulated by KDM1A (LSD1). KDM1A is overexpressed in several tumor types, thus representing an emerging target for the development of novel cancer therapeutics. We have previously described (Part 1, DOI 10.1021.acs.jmedchem.6b01018) the identification of thieno[3,2-b]pyrrole-5-carboxamides as novel reversible inhibitors of KDM1A, whose preliminary exploration resulted in compound 2 with biochemical IC50 = 160 nM. We now report the structure-guided optimization of this chemical series based on multiple ligand/KDM1A-CoRest cocrystal structures, which led to several extremely potent inhibitors. In particular, compounds 46, 49, and 50 showed single-digit nanomolar IC50 values for in vitro inhibition of KDM1A, with high selectivity in secondary assays. In THP-1 cells, these compounds transcriptionally affected the expression of genes regulated by KDM1A such as CD14, CD11b, and CD86. Moreover, 49 and SO showed a remarkable anticlonogenic cell growth effect on MLL-AF9 human leukemia cells.

  DOI：

  10.1021/acs.jmedchem.6b01019
• 作为产物：
  描述：

  N-叔丁氧羰基-4-哌啶酮 、 对氨基苯酚 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以84%的产率得到tert-butyl 4-(4-hydroxyanilino)piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] THIENOPYRROLES AS HISTONE DEMETHYLASE INHIBITORS
  [FR] THIÉNOPYRROLES COMME INHIBITEURS DE L'HISTONE DÉMÉTHYLASE

  摘要：

  公开号：

  WO2016034946A3

文献信息

• Thienopyrroles as histone demethylase inhibitors
  申请人：IEO - Istituto Europeo di Oncologia Srl

  公开号：EP2993175A1

  公开（公告）日：2016-03-09

  The present invention relates to thienopyrrole derivatives, wherein R, R1, R2 and R3 are as defined in the specification, pharmaceutical compositions containing such compounds and to their use in therapy.

  本发明涉及噻吩吡咯衍生物（其中 R、R1、R2 和 R3 如说明书中所定义）、含有此类化合物的药物组合物及其在治疗中的用途。
• THIENOPYRROLES AS HISTONE DEMETHYLASE INHIBITORS
  申请人：Istituto Europeo di Oncologia S.r.l.

  公开号：EP3189059A2

  公开（公告）日：2017-07-12
• WO2024054955A1
  申请人：——

  公开号：——

  公开（公告）日：——
• Thieno[3,2-<i>b</i>]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 2: Structure-Based Drug Design and Structure–Activity Relationship
  作者：Paola Vianello、Luca Sartori、Federica Amigoni、Anna Cappa、Giovanni Fagá、Raimondo Fattori、Elena Legnaghi、Giuseppe Ciossani、Andrea Mattevi、Giuseppe Meroni、Loris Moretti、Valentina Cecatiello、Sebastiano Pasqualato、Alessia Romussi、Florian Thaler、Paolo Trifiró、Manuela Villa、Oronza A. Botrugno、Paola Dessanti、Saverio Minucci、Stefania Vultaggio、Elisa Zagarrí、Mario Varasi、Ciro Mercurio

  DOI：10.1021/acs.jmedchem.6b01019

  日期：2017.3.9

  The balance of methylation levels at histone H3 lysine 4 (H3K4) is regulated by KDM1A (LSD1). KDM1A is overexpressed in several tumor types, thus representing an emerging target for the development of novel cancer therapeutics. We have previously described (Part 1, DOI 10.1021.acs.jmedchem.6b01018) the identification of thieno[3,2-b]pyrrole-5-carboxamides as novel reversible inhibitors of KDM1A, whose preliminary exploration resulted in compound 2 with biochemical IC50 = 160 nM. We now report the structure-guided optimization of this chemical series based on multiple ligand/KDM1A-CoRest cocrystal structures, which led to several extremely potent inhibitors. In particular, compounds 46, 49, and 50 showed single-digit nanomolar IC50 values for in vitro inhibition of KDM1A, with high selectivity in secondary assays. In THP-1 cells, these compounds transcriptionally affected the expression of genes regulated by KDM1A such as CD14, CD11b, and CD86. Moreover, 49 and SO showed a remarkable anticlonogenic cell growth effect on MLL-AF9 human leukemia cells.
• [EN] THIENOPYRROLES AS HISTONE DEMETHYLASE INHIBITORS<br/>[FR] THIÉNOPYRROLES COMME INHIBITEURS DE L'HISTONE DÉMÉTHYLASE
  申请人：ISTITUTO EUROP DI ONCOLOGIA S R L

  公开号：WO2016034946A3

  公开（公告）日：2016-05-12