tert-butyl 4-((4-chlorophenyl)carbamoyl)piperidine-1-carboxylate | 859154-43-1

• 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-chlorophenyl)carbamoyl)piperidine-1-carboxylate
• 英文别名: tert-Butyl 4-{[(4-chlorophenyl)amino]carbonyl}piperidine-1-carboxylate；tert-butyl 4-[(4-chlorophenyl)carbamoyl]piperidine-1-carboxylate
• CAS: 859154-43-1
• 化学式: C₁₇H₂₃ClN₂O₃
• 分子量: 338.834
• InChiKey: HKBWLXCDHPJXLI-UHFFFAOYSA-N

物化性质

• 沸点：
  499.6±40.0 °C(Predicted)
• 密度：
  1.231±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 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：

  tert-butyl 4-((4-chlorophenyl)carbamoyl)piperidine-1-carboxylate 在 碳酸氢钠 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 methyl (4-((4-chlorophenyl)carbamoyl)piperidine-1-carbonyl)-L-leucinate
  参考文献：
  名称：

  Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles

  摘要：

  The potential of specific proteasome inhibitors to act as anti-cancer agents has attracted intensive investigations. The proteasome can be covalently inhibited by epoxyketone derivatives via a two-step reaction. Several computational approaches have been developed to mimic the covalent binding event. Compound 1 composed of a six-membered heterocyclic ring was designed by using covalent docking. With a possible different binding mode from the clinical compound Carfilzomib, it occupied the 55 pocket of 20S proteasome and showed favorable inhibitory activity. Subsequently optimization and evaluation were taken place. Among these compounds, 11h demonstrated extraordinary in vitro inhibitory activity and selectivity, and good in vivo proteasome inhibitory activity, a favorable pharmacokinetic profile and xenograft tumor inhibition. The possible binding pattern of compound 11h against proteasome was further fully explored via calculations, providing a theoretical basis for finding potent proteasome inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.064
• 作为产物：
  描述：

  1-Boc-4-哌啶甲酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 tert-butyl 4-((4-chlorophenyl)carbamoyl)piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] MODULATORS OF VASOPRESSIN RECEPTORS WITH THERAPEUTIC POTENTIAL
  [FR] MODULATEURS DES RÉCEPTEURS DE LA VASOPRESSINE À POUVOIR THÉRAPEUTIQUE

  摘要：

  提供了包含哌嗪、哌啶、螺环呋喃哌啶及其类似物的化合物，这些化合物是利钠素受体的调节剂，如正向变构调节剂，可以调节一个或多个亚类别的利钠素受体。这些化合物可以是一个或多个亚类别的利钠素受体的选择性调节剂。本发明的化合物可用于治疗需要调节利钠素受体的情况。

  公开号：

  WO2014127350A1

文献信息

• Discovery of Aryl Formyl Piperidine Derivatives as Potent, Reversible, and Selective Monoacylglycerol Lipase Inhibitors
  作者：Zhuoer Zhi、Wenting Zhang、Jingchun Yao、Yanguo Shang、Qingjing Hao、Zhong Liu、Yushan Ren、Jie Li、Guimin Zhang、Jinxin Wang

  DOI：10.1021/acs.jmedchem.9b02137

  日期：2020.6.11

  creatively identify a new key anchoring point for the development of new MAGL inhibitors. Furthermore, in vivo evaluation innovatively revealed that this reversible inhibitor 36 significantly ameliorated depressive-like behaviors induced by reserpine. To the best of our knowledge, this is the first time that reversible inhibitors of MAGL were developed to support MAGL as a potential therapeutic target for

  当前大多数的单酰基甘油脂肪酶（MAGL）抑制剂通过不可逆的作用机理发挥作用，引起一系列副作用。在此，从不可逆抑制剂开始，合成了25种化合物并进行了体外MAGL抑制评估，其中，化合物36表现出最强的抑制活性（IC 50 = 15 nM）。至关重要的是，对接研究表明，米-氯基取代的苯胺片段占用由Val191，Tyr194，Val270，和Lys273的侧链，其创造性标识新的关键点的锚定为新MAGL抑制剂发展包围的疏水副袋中。此外，体内评估创新地揭示了这种可逆抑制剂36显着改善了利血平引起的抑郁样行为。据我们所知，这是首次开发可逆性MAGL抑制剂来支持MAGL作为抑郁症的潜在治疗靶标。
• Compounds useful in therapy
  申请人：Bryans Stephen Justin

  公开号：US20050154024A1

  公开（公告）日：2005-07-14

  Compounds of formula (I), or pharmaceutically acceptable derivatives thereof, wherein: X represents —[CH 2 ] a —R or —[CH 2 ] a —O—[CH 2 ] b —R; a represents a number selected from 0 to 6; b represents a number selected from 0 to 6; R represents H, CF 3 or Het; Het represents an optionally substituted 5- or 6-membered saturated, partially saturated or aromatic heterocyclic ring; Y represents one or more substituents independently selected from —[O] c —[CH 2 ] d —R 1 , which may be the same or different at each occurrence; c at each occurrence independently represents a number selected from 0 or 1; d at each occurrence independently represents a number selected from 0 to 6; R 1 at each occurrence independently represents H, halo, CF 3 , CN or Het 1 ; Het 1 at each occurrence independently represents a 5- or 6-membered unsaturated heterocyclic ring; V represents a direct link or —O—; Ring A represents an optionally substituted 5- to 7-membered saturated heterocyclic ring, or a phenylene group; Q represents a direct link or —N(R 2 )—; R 2 represents hydrogen or C 1-6 alkyl; Z represents —[O] e —[CH 2 ] f —R 3 , a phenyl ring (optionally fused to a benzene ring or Het 2 , and the group as a whole being optionally substituted), or Het 3 (optionally fused to an benzene ring or Het 4 , and the group as a whole being optionally substituted); R 3 represents C 1-6 alkyl (optionally substituted), C 3-6 cycloalkyl, C 3-6 cycloalkenyl, phenyl (optionally substituted), Het 5 or NR 4 R 5 ; e represents a number selected from 0 or 1; f represents a number selected from 0 to 6; Het 2 and Het 5 independently represent optionally substituted 5- or 6-membered saturated, partially saturated or aromatic heterocyclic rings; Het 3 represents an optionally substituted 4 to 6-membered saturated, partially saturated or aromatic heterocyclic ring; Het 4 represents an optionally substituted 6-membered aromatic heterocyclic ring; R 4 and R 5 independently represent optionally substituted C 1-6 alkyl, C 1-6 alkyloxy, C 3-8 cycloalkyl (optionally fused to C 3-8 cycloalkyl), Het 6 , or hydrogen; Het 6 represents an optionally substituted 5- or 6-membered saturated, partially saturated or aromatic heterocyclic ring; are useful for treating a disorder for which a V1 a antagonist is indicated.

  式(I)的化合物，或其药学上可接受的衍生物，其中： X代表—[CH 2 ] a —R或—[CH 2 ] a —O—[CH 2 ] b —R；a代表从0到6中选择的数字；b代表从0到6中选择的数字； R代表H，CF 3 或Het；Het代表一个可选择取代的5-或6-成员饱和、部分饱和或芳香杂环环； Y代表一个或多个取代基，独立地选择自—[O] c —[CH 2 ] d —R 1 ，每次出现时可能相同也可能不同；c在每次出现时独立地代表从0或1中选择的数字；d在每次出现时独立地代表从0到6中选择的数字； R 1 在每次出现时独立地代表H，卤素，CF 3 ，CN或Het 1 ； Het 1 在每次出现时独立地代表一个5-或6-成员不饱和杂环环；V代表一个直链或—O—；环A代表一个可选择取代的5-到7-成员饱和杂环环，或一个苯基团； Q代表一个直链或—N(R 2 )—； R 2 代表氢或C 1-6 烷基； Z代表—[O] e —[CH 2 ] f —R 3 ，一个苯环（可选择与苯环或Het 2 融合，并且整体作为可选择取代的团），或Het 3 （可选择与苯环或Het 4 融合，并且整体作为可选择取代的团）； R 3 代表C 1-6 烷基（可选择取代），C 3-6 环烷基，C 3-6 环烯基，苯基（可选择取代），Het 5 或NR 4 R 5 ；e代表从0或1中选择的数字；f代表从0到6中选择的数字； Het 2 和Het 5 独立地代表可选择取代的5-或6-成员饱和、部分饱和或芳香杂环环； Het 3 代表一个可选择取代的4到6-成员饱和、部分饱和或芳香杂环环； Het 4 代表一个可选择取代的6-成员芳香杂环环； R 4 和R 5 独立地代表可选择取代的C 1-6 烷基，C 1-6 烷氧基，C 3-8 环烷基（可与C 3-8 环烷基融合），Het 6 ，或氢； Het 6 代表一个可选择取代的5-或6-成员饱和、部分饱和或芳香杂环环；适用于治疗需要V1 a 拮抗剂的紊乱。
• Optimization of piperidine constructed peptidyl derivatives as proteasome inhibitors
  作者：Yanmei Zhao、Lei Xu、Jiankang Zhang、Mengmeng Zhang、Jingyi Lu、Ruoyu He、Jianjun Xi、Rangxiao Zhuang、Jia Li、Yubo Zhou

  DOI：10.1016/j.bmc.2020.115867

  日期：2021.1

  A series of non-covalent piperidine-containing peptidyl derivatives with various substituents at side chains of different residues were designed, synthesized and evaluated as proteasome inhibitors. After proteasome inhibitory evaluations of all the synthesized target compounds, selected ones were tested for their anti-proliferation activities against three multiple myeloma (MM) cell lines. 8 analogues

  一系列在不同残基的侧链上具有各种取代基的非共价含哌啶肽基衍生物被设计、合成并评估为蛋白酶体抑制剂。在对所有合成的目标化合物进行蛋白酶体抑制评估后，测试所选化合物对三种多发性骨髓瘤 (MM) 细胞系的抗增殖活性。8 种类似物显示出比卡非佐米更有效的活性，最有前途的化合物24对 20S 蛋白酶体的IC 50值为 0.8±0.2 nM，对RPMI 82926 的IC 50值为 8.42±0.74 nM、7.14±0.52 nM、14.20±1.08 nM MM.1S 细胞系，分别。此外，代表性化合物24的抗癌活性机制被进一步调查。RPMI-8226 细胞的凋亡是通过积累多聚泛素和诱导 caspase 和 PARP 的裂解来实现的。此外，优化后化合物24在大鼠血浆中的半衰期延长，这将有助于提高该系列衍生物的体内活性。所有研究证实，含哌啶的非共价蛋白酶体抑制剂可能是抗 MM 药物开发的潜在线索。
• Triazolyl piperidine arginine vasopressin receptor modulators
  申请人：——

  公开号：US07745630B2

  公开（公告）日：2010-06-29

  Compounds of formula (I), or pharmaceutically acceptable derivatives thereof, wherein: Z, O, A, V, Y and Y′ are as defined herein; are useful for treating dysmenorreah.

  式(I)的化合物或其药学上可接受的衍生物，其中：Z、O、A、V、Y和Y'如本文所定义；适用于治疗痛经。
• Compounds Useful In Therapy
  申请人：Bryans Justin Stephen

  公开号：US20100317652A1

  公开（公告）日：2010-12-16

  The present invention provides compounds of formula (I), or pharmaceutically acceptable derivatives thereof wherein the variables Z, Q, Ring A, V, X, Y and Y′ are as defined herein, and pharmaceutical compositions comprising these compounds. The compounds of formula (I) and pharmaceutical compositions comprising them are useful for treating a disorder for which a V1a antagonist is indicated, in particular, dysmenorrhoea.

  本发明提供了式(I)的化合物或其药学上可接受的衍生物，其中变量Z，Q，环A，V，X，Y和Y'如此定义，并且包含这些化合物的药物组合物。式(I)的化合物和包含它们的药物组合物可用于治疗需要V1a拮抗剂的紊乱，特别是痛经。