4-(4-氟苯磺酰基)-哌啶-1-羧酸叔丁酯 | 226398-50-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-(4-氟苯磺酰基)-哌啶-1-羧酸叔丁酯
• 中文别名: 4-[(4-氟苯基)磺酰基]-1-哌啶甲酸叔丁酯
• 英文名称: tert-butyl 4-((4-fluorophenyl)sulfonyl)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-[(4-fluorophenyl)sulfonyl]piperidine-1-carboxylate；N-tert-butoxycarbonyl-4-(4-fluorophenylsulfonyl)piperidine；tert-butyl 4-(4-fluoro-benzenesulfonyl)-piperidine-1-carboxylate；1-tert-Butoxycarbonyl-4-(4-fluorophenylsulfonyl)piperidine；N-BOC 4-(4-fluorophenylsulfonyl)piperidine；4-(4-Fluoro-benzenesulfonyl)-piperidine-1-carboxylic acid tert-butyl ester；tert-butyl 4-(4-fluorophenyl)sulfonylpiperidine-1-carboxylate
• CAS: 226398-50-1
• 化学式: C₁₆H₂₂FNO₄S
• 分子量: 343.419
• InChiKey: QQEOFGKCYHRZIQ-UHFFFAOYSA-N

物化性质

• 熔点：
  167-169℃
• 沸点：
  473.6±45.0 °C(Predicted)
• 密度：
  1.243

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 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：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  4-(4-氟苯磺酰基)-哌啶-1-羧酸叔丁酯 在 盐酸 、 正丁基锂 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 、 乙腈 为溶剂， 反应 1.0h， 生成 4-({1-[2-(2,4-difluorophenyl)ethyl]-4-fluoropiperidin-4-yl}sulfonyl)benzonitrile
  参考文献：
  名称：

  4-Fluorosulfonylpiperidines: Selective 5-HT2A ligands for the treatment of insomnia

  摘要：

  Incorporation of fluorine at the 4-position of an existing series of sulfonyl piperidine 5-HT2A antagonists gave compounds with increased selectivity over the IKr potassium channel. This work led to the identification of 3b, a compound that gave no increase in QT(c) in the anesthetized dog up to plasma levels as high as 148 mu M. Furthermore, 3b has been shown to increase slow-wave sleep bout duration and to decrease the number of awakenings in rats, indicating the potential utility of 5-HT2A antagonists in the treatment of insomnia. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.104
• 作为产物：
  描述：

  1-氟-4-[(4-氟苯基)二硫烷基]苯 在 aluminum oxide 、 Oxone 、 三丁基膦 作用下， 以 四氢呋喃 、 氯仿 、 水 为溶剂， 反应 66.0h， 生成 4-(4-氟苯磺酰基)-哌啶-1-羧酸叔丁酯
  参考文献：
  名称：

  4-(Phenylsulfonyl)piperidines:  Novel, Selective, and Bioavailable 5-HT_2A Receptor Antagonists

  摘要：

  On the basis of a spirocyclic ether screening lead, a series of acyclic sulfones have been identifed as high-affinity, selective 5-HT2A receptor antagonists. Bioavailability lacking in the parent, 1-(2-(2,4-difluorophenyl)ethyl)-4-(phenylsulfonyl)piperidine (12), was introduced by using stability toward rat liver microsomes as a predictor of bioavailability. By this means, the 4-cyano- and 4-carboxamidophenylsulfonyl derivatives 26 and 31 were identified as orally bioavailable, brain-penetrant analogues suitable for evaluation in animal models. Bioavailability was also attainable by N substitution leading to the N-phenacyl derivative 35. IKr activity detected through counterscreening was reduced to insignificant levels in vivo with the latter compound.

  DOI：

  10.1021/jm011030v

文献信息

• Cyclic amine compounds as CCR5 antagonists
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06562978B1

  公开（公告）日：2003-05-13

  A compound of formula (I) (wherein R1 is a hydrogen atom, a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, R2 is a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, or R1 and R2 may combine to each other together with A to form a heterocyclic group which may be substituted; A is N or N+—R5.Y−(R5 is a hydrocarbon group; Y− is a counter anion); R3 is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; n is 0 or 1; R4 is a hydrogen atom, a hydrocarbon group which may be substituted, a heterocyclic group which may be substituted, an alkoxy group which may be substituted, an aryloxy group which may be substituted, or an amino group which may be substituted, E is a divalent aliphatic hydrocarbon group which may be substituted by group(s) other than oxo; G1 is a bond, CO or SO2; G2 is CO, SO2, NHCO, CONH or OCO; J is methine or a nitrogen atom; and each of Q and R is a bond or a divalent C1-3 aliphatic hydrocarbon which may be substituted; provided that J is methine when G2 is OCO, that one of Q and R is not a bond when the other is a bond and that each of Q and R is not substituted by oxo group(s) when G1 is a bond) or a salt thereof has a potent CCR5 antagonistic activity and can be advantageously used for the treatment or prevention of infectious disease of various HIV in human (e.g. AIDS).

  式（I）的化合物（其中R1是氢原子，可能被取代的碳氢基团，可能被取代的非芳香杂环基团，R2是可能被取代的碳氢基团，可能被取代的非芳香杂环基团，或R1和R2可以彼此结合与A一起形成可能被取代的杂环基团；A是N或N+—R5.Y−（R5是碳氢基团；Y−是一个对离子）；R3是可能被取代的环烃基团或可能被取代的杂环基团；n为0或1；R4是氢原子，可能被取代的碳氢基团，可能被取代的杂环基团，可能被取代的烷氧基团，可能被取代的芳基氧基团，或可能被取代的氨基团；E是可能被除氧以外的基团取代的二价脂肪族碳氢基团；G1是键，CO或SO2；G2是CO，SO2，NHCO，CONH或OCO；J是亚甲基或氮原子；Q和R中的每一个是键或可能被取代的二价C1-3脂肪族碳氢基团；条件是当G2为OCO时J为亚甲基，当另一个为键时Q和R中的一个不是键，当G1为键时Q和R中的每一个都不被氧基取代）或其盐具有强大的CCR5拮抗活性，并可优势用于治疗或预防人类体内各种HIV引起的传染病（例如艾滋病）。
• Discovery of M-1121 as an Orally Active Covalent Inhibitor of Menin-MLL Interaction Capable of Achieving Complete and Long-Lasting Tumor Regression
  作者：Meng Zhang、Angelo Aguilar、Shilin Xu、Liyue Huang、Krishnapriya Chinnaswamy、Taryn Sleger、Bo Wang、Stefan Gross、Brandon N. Nicolay、Sebastien Ronseaux、Kaitlin Harvey、Yu Wang、Donna McEachern、Paul D. Kirchhoff、Zhaomin Liu、Jeanne Stuckey、Adriana E. Tron、Tao Liu、Shaomeng Wang

  DOI：10.1021/acs.jmedchem.1c00789

  日期：2021.7.22

  protein–protein interaction is being pursued as a new therapeutic strategy for the treatment of acute leukemia carrying MLL-rearrangements (MLLr leukemia). Herein, we report M-1121, a covalent and orally active inhibitor of the menin-MLL interaction capable of achieving complete and persistent tumor regression. M-1121 establishes covalent interactions with Cysteine 329 located in the MLL binding pocket

  针对menin-MLL 蛋白-蛋白相互作用作为治疗携带MLL 重排的急性白血病（MLLr 白血病）的一种新的治疗策略正在被寻求。在此，我们报告了 M-1121，一种能够实现完全和持续的肿瘤消退的 menin-MLL 相互作用的共价和口服活性抑制剂。M-1121 与位于 menin 的 MLL 结合口袋中的半胱氨酸 329 建立共价相互作用，并有效抑制携带 MLL 易位的急性白血病细胞系的生长，而在具有野生型 MLL 的细胞系中没有活性。与作用机制一致，M-1121 驱动HOXA9和MEIS1的剂量依赖性下调MLL 重排的 MV4;11 白血病细胞系中的基因表达。M-1121 具有口服生物利用度，在体内显示出有效的抗肿瘤活性，在 MLL 重排白血病的皮下和播散模型中，在耐受剂量下观察到肿瘤消退。总之，我们的研究结果支持开发一种口服活性共价门宁抑制剂作为 MLLr 白血病的新疗法。
• TETRAHYDROPYRIDOPYRAZINES MODULATORS OF GPR6
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20150175602A1

  公开（公告）日：2015-06-25

  The present invention provides compounds of formula I: which are useful as modulators of GPR6, pharmaceutical compositions thereof, methods for treatment of conditions associated with GPR6, processes for making the compounds and intermediates thereof.

  本发明提供了式I化合物： 这些化合物作为GPR6调节剂具有用途，包括相关的药物组合物、治疗与GPR6相关病症的方法、制备这些化合物及其中间体的工艺。
• [EN] 4-ARYLSULPHONYLPIPERIDINE DERIVATIVES FOR ANTAGONISM OF THE 5-HT2A RECEPTOR<br/>[FR] DERIVES DE 4-ARYLSULPHONYLPIPERIDINE POUR L'ANTAGONISME DU RECEPTEUR DE 5-HT2A
  申请人：MERCK SHARP & DOHME

  公开号：WO2004101518A1

  公开（公告）日：2004-11-25

  Compounds of formula (I): are selective antagonists of the 5-HT2A receptor, and hence are useful in treatment of adverse conditions at the central nervous system, such as sleep disorders and schizophrenia.

  式(I)的化合物是5-HT2A受体的选择性拮抗剂，因此在治疗中枢神经系统的不良症状，如睡眠障碍和精神分裂症方面具有用处。
• [EN] PYRIDOPYRAZINES MODULATORS OF GPR6<br/>[FR] MODULATEURS PYRIDOPYRAZINES DE GPR6
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2015123505A1

  公开（公告）日：2015-08-20

  The present invention provides compounds of formula (I): [Formula should be entered here] which are useful as modulators of GPR6, pharmaceutical compositions thereof, methods for treatment of conditions associated with GPR6, processes for making the compounds and intermediates thereof.

  本发明提供了式（I）的化合物：[应在此处输入公式]，其作为GPR6调节剂是有用的，以及其药物组合物，治疗与GPR6相关疾病的方法，制备该化合物及其中间体的过程。