4-cyclohexylbutyl 2-oxopyridine-1-carboxylate | 1439367-44-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-cyclohexylbutyl 2-oxopyridine-1-carboxylate
• 英文别名: 4-Cyclohexylbutyl-2-oxopyridine-1-carboxylate
• CAS: 1439367-44-8
• 化学式: C₁₆H₂₃NO₃
• 分子量: 277.364
• InChiKey: USTJSFNCMRPLBW-UHFFFAOYSA-N

物化性质

• 沸点：
  392.6±25.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-cyclohexylbutyl 2-oxopyridine-1-carboxylate 、 [(S)-2-oxoazetidin-3-yl]ammonium acetate 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以58%的产率得到ARN726
  参考文献：
  名称：

  [EN] CARBAMATE DERIVATIVES OF LACTAM BASED N-ACYLETHANOLAMINE ACID AMIDASE (NAAA) INHIBITORS
  [FR] DÉRIVÉS DE CARBAMATE D'INHIBITEURS D'AMIDASE ACIDE DE N-ACYLÉTHANOLAMINE (NAAA) À BASE DE LACTAME

  摘要：

  公开号：

  WO2014144836A3
• 作为产物：
  描述：

  碳酸二(2-吡啶)酯 、 4-环己基-1-丁醇 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 4-cyclohexylbutyl 2-pyridyl carbonate 、 4-cyclohexylbutyl 2-oxopyridine-1-carboxylate
  参考文献：
  名称：

  强大的α-氨基-β-内酰胺氨基甲酸酯作为NAAA抑制剂。合成与结构-活性关系（SAR）研究

  摘要：

  4-环己基丁基-N -[（S）-2-氧杂氮杂环丁-3-基]氨基甲酸酯（3b）是一种有效的，选择性的和系统性的细胞内NAAA活性抑制剂，可在动物模型中产生深远的抗炎作用。在当前的工作中，我们描述了对3-氨基氮杂环丁烷-2-one衍生物的结构-活性关系（SAR）研究，该研究导致了3b的鉴定，并扩展了这些研究以阐明获得有效的结构和立体化学特征。 NAAA抑制。关于2-氧代-3-氮杂环丁烷基环的β-位取代的影响以及氨基甲酸酯侧链的大小和形状的影响的研究导致了3ak的发现。，一种人类NAAA的新型抑制剂，相对于3b而言，它具有改善的理化和类药物特性。这种有利的特性以及3b氨基甲酸酯链的结构多样性，使该化合物成为研究NAAA抑制剂作为治疗疼痛和炎症的潜力的有前途的新工具。

  DOI：

  10.1016/j.ejmech.2016.01.046

文献信息

• Progress in the development of β-lactams as N-Acylethanolamine Acid Amidase (NAAA) inhibitors: Synthesis and SAR study of new, potent N-O-substituted derivatives
  作者：R. Petracca、S. Ponzano、S.M. Bertozzi、O. Sasso、D. Piomelli、T. Bandiera、F. Bertozzi

  DOI：10.1016/j.ejmech.2016.11.039

  日期：2017.1

  serine-derived β-lactams as potent and systemically active inhibitors of NAAA activity. Aiming to expand the SAR study around this class of compounds, we investigated the effect of the substitution on the endocyclic nitrogen by designing and synthesizing a series of N-substituted β-lactams. The present work describes the synthesis of new N-O-alkyl and N-O-aryl substituted β-lactams and reports the results

  由于提高内源性生物活性脂质棕榈酰乙醇酰胺（PEA）的水平而产生的抗炎作用导致设想将N-乙酰乙醇胺酸酰胺酶（NAAA）（主要负责PEA降解的半胱氨酸水解酶）作为小分子抑制剂的诱人靶标。我们小组以前的工作将丝氨酸衍生的β-内酰胺确定为NAAA活性的强效和全身活性抑制剂。为了扩大围绕此类化合物的SAR研究，我们通过设计和合成一系列N取代的β-内酰胺，研究了取代对内环氮的影响。本工作描述了新的N - O-烷基和N - O的合成。-芳基取代的β-内酰胺类化合物，并报道了结构活性关系（SAR）研究的结果，导致发现了一种新颖的单位一位数的纳摩尔NAAA抑制剂（37）。化合物37在体外显示出通过催化半胱氨酸的S-酰化来抑制人NAAA ，并且相对于人酸性神经酰胺酶（与NAAA结构相关的半胱氨酸酰胺酶）显示出非常好的选择性。体内初步研究表明，在角叉菜胶诱导的炎症小鼠模型中，局部给药的化合物37可减轻爪水肿和热
• [EN] DISUBSTITUTED BETA-LACTONES AS INHIBITORS OF N-ACYLETHANOLAMINE ACID AMIDASE (NAAA)<br/>[FR] BÊTA-LACTONES DISUBSTITUÉS EN TANT QU'INHIBITEURS DE L'AMIDASE ACIDE DE N-ACYLÉTHANOLAMINE (NAAA)
  申请人：UNIV CALIFORNIA

  公开号：WO2013078430A1

  公开（公告）日：2013-05-30

  The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.

  本发明提供了用于抑制N-酰乙醇胺酸酰胺酶（NAAA）的化合物和药物组合物。考虑到抑制NAAA是一种维持棕榈酰乙醇胺（PEA）和油酰乙醇胺（OEA）水平的方法，这两种物质是NAAA的底物，在特征为PEA和OEA浓度降低的情况下。该发明还提供了治疗炎症性疾病和疼痛以及其他与降低PEA和OEA水平相关的疾病的方法。
• Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
  申请人：The Regents of the University of California

  公开号：US09353075B2

  公开（公告）日：2016-05-31

  The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.

  本发明提供了用于抑制N-酰基乙醇胺酸酰胺酶（NAAA）的化合物和药物组合物。考虑到抑制NAAA是一种维持棕榈酰乙醇胺（PEA）和油酰乙醇胺（OEA）水平的方法，在特征为PEA和OEA浓度降低的情况下。该发明还提供了治疗炎症性疾病和疼痛以及其他与降低PEA和OEA水平相关的紊乱的方法。
• CARBAMATE DERIVATIVES OF LACTAM BASED N-ACYLETHANOLAMINE ACID AMIDASE (NAAA) INHIBITORS
  申请人：The Regents of the University of California

  公开号：US20160068482A1

  公开（公告）日：2016-03-10

  Described herein are compounds and pharmaceutical compositions which inhibit N-acylethanolamine acid amidase (NAAA). Described herein are methods for synthesizing the compounds set forth herein and methods for formulating these compounds as pharmaceutical compositions which include these compounds. Also described herein are methods of inhibiting NAAA in order to sustain the levels of palmitoylethanolamide (PEA) and other N-acylethanolamines (NAE) that are substrates for NAAA, in conditions characterized by reduced concentrations of NAE. Also, described here are methods of treating and ameliorating pain, inflammation, inflammatory diseases, and other disorders in which modulation of fatty acid ethanolamides is clinically or therapeutically relevant or in which decreased levels of NAE are associated with the disorder.

  本文描述了一些化合物和药物组成物，它们可以抑制N-酰基乙醇胺酸酰化酶（NAAA）。本文还描述了合成这些化合物的方法，以及将它们制成药物组成物的方法。同时，本文还描述了抑制NAAA以维持棕榈酰乙醇胺（PEA）和其他N-酰基乙醇胺（NAE）的水平的方法，这些物质是NAAA的底物，并且在NAE浓度降低的情况下有用。此外，本文还描述了治疗和缓解疼痛、炎症、炎症性疾病和其他疾病的方法，这些疾病中脂肪酸乙醇胺的调节在临床或治疗上是相关的，或者NAE的浓度降低与该疾病有关。
• Synthesis, Biological Evaluation, and 3D QSAR Study of 2-Methyl-4-oxo-3-oxetanylcarbamic Acid Esters as <i>N</i>-Acylethanolamine Acid Amidase (NAAA) Inhibitors
  作者：Stefano Ponzano、Anna Berteotti、Rita Petracca、Romina Vitale、Luisa Mengatto、Tiziano Bandiera、Andrea Cavalli、Daniele Piomelli、Fabio Bertozzi、Giovanni Bottegoni

  DOI：10.1021/jm501455s

  日期：2014.12.11

  N-(2-Oxo-3-oxetanyl)carbamic acid esters have recently been reported to be noncompetitive inhibitors of the N-acylethanolamine acid amidase (NAAA) potentially useful for the treatment of pain and inflammation. In the present study, we further explored the structure-activity relationships of the carbamic acid ester side chain of 2-methyl-4-oxo-3-oxetanylcarbamic acid ester derivatives. Additional favorable features in the design of potent NAAA inhibitors have been found together with the identification of a single digit nanomolar inhibitor. In addition, we devised a 3D QSAR using the atomic property field method. The model turned out to be able to account for the structural variability and was prospectively validated by designing, synthesizing, and testing novel inhibitors. The fairly good agreement between predictions and experimental potency values points to this 3D QSAR model as the first example of quantitative structure-activity relationships in the field of NAAA inhibitors.