N-(p-tolyl)-4-oxo-4H-chromene-3-carboxamide | 1268279-39-5

• 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: N-(p-tolyl)-4-oxo-4H-chromene-3-carboxamide
• 英文别名: N-(4-methylphenyl)-4-oxo-4H-1-benzopyran-3-carboxamide；4-oxo-N-p-tolyl-4H-chromene-3-carboxamide；N-(4-methylphenyl)-4-oxochromene-3-carboxamide
• CAS: 1268279-39-5
• 化学式: C₁₇H₁₃NO₃
• 分子量: 279.295
• InChiKey: ZPHGXJAOXHSRAX-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：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  色酮-3-甲酸 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 N-(p-tolyl)-4-oxo-4H-chromene-3-carboxamide
  参考文献：
  名称：

  通过棘手的化学方法发现了两类新的强力单胺氧化酶-B抑制剂。

  摘要：

  发现用于治疗神经退行性疾病例如阿尔茨海默氏病和帕金森氏病的有效和选择性的单胺氧化酶-B抑制剂仍然是一项艰巨的任务。在本文中，我们报告发现了基于苯并二氢吡喃-2,4-二酮和苯并三苯甲酮-3-甲酰胺骨架的两类新的有效和选择性MAO-B抑制剂。

  DOI：

  10.1039/c4cc08798d

文献信息

• Discovery of novel A3 adenosine receptor ligands based on chromone scaffold
  作者：Alexandra Gaspar、Joana Reis、Sonja Kachler、Silvia Paoletta、Eugenio Uriarte、Karl-Norbert Klotz、Stefano Moro、Fernanda Borges

  DOI：10.1016/j.bcp.2012.03.007

  日期：2012.7

  has been developed. Accordingly, two series of novel chromone carboxamides placed at positions C2 (compounds 2-13) and C3 (compounds 15-26) of the gamma-pyrone ring were synthesized using chromone carboxylic acids (compounds 1 or 14) as starting materials. From this study and on the basis of the obtained structure-activity relationships it was concluded that the chromone carboxamide scaffold represent

  已经开发了一个致力于发现新化学实体（NCE）作为AR配体的项目，该配体包含苯并-γ-吡喃酮[（4H）-1-苯并吡喃-4-酮]子结构。因此，使用色酮羧酸（化合物1或14）作为起始原料，合成了位于γ-吡喃酮环的位置C2（化合物2-13）和C3（化合物15-26）的两个新的色酮羧酰胺系列。从这项研究中，并在获得的结构-活性关系的基础上，得出的结论是，色酮羧酰胺支架代表了一类新型的AR配体。最显着的色酮是对A3AR表现出更好亲和力的化合物21和26（分别为Ki = 3680 nM和Ki = 3750 nM）。受体驱动的分子建模研究提供了有关色酮的结合/选择性数据的信息。
• Discovery of two new classes of potent monoamine oxidase-B inhibitors by tricky chemistry
  作者：F. Cagide、T. Silva、J. Reis、A. Gaspar、F. Borges、L. R. Gomes、J. N. Low

  DOI：10.1039/c4cc08798d

  日期：——

  The discovery of potent and selective monoamine oxidase-B inhibitors for the management of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is still a challenging endeavor. Herein, we report the discovery of two new classes of potent and selective MAO-B inhibitors based on chromane-2,4-dione and chromone-3-carboxamide scaffolds.

  发现用于治疗神经退行性疾病例如阿尔茨海默氏病和帕金森氏病的有效和选择性的单胺氧化酶-B抑制剂仍然是一项艰巨的任务。在本文中，我们报告发现了基于苯并二氢吡喃-2,4-二酮和苯并三苯甲酮-3-甲酰胺骨架的两类新的有效和选择性MAO-B抑制剂。
• Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors
  作者：Alexandra Gaspar、Joana Reis、André Fonseca、Nuno Milhazes、Dolores Viña、Eugenio Uriarte、Fernanda Borges

  DOI：10.1016/j.bmcl.2010.11.128

  日期：2011.1

  Monoamine oxidase (MAO) is an enzyme, present in mammals in two isoforms MAO-A and MAO-B. These isoforms have a crucial role in neurotransmitters metabolism, representing an attractive drug target in the therapy of neurodegenerative diseases (MAO-B) and depression (MAO-A). In this context, our work has been focused on the discovery of new chemical entities (NCEs) for MAO inhibition, based on the development of chromone carboxamides. Chromone derivatives with a carboxamide function located in position 2- and 3- of the benzo-gamma-pyrone core, (compounds 2-6 and 8-12) were synthesized, with moderate/good yields, by a one-pot condensation reaction using phosphonium salts as coupling reagents. The synthetic compounds were screened towards human MAO isoforms (hMAO) to evaluate their potency and selectivity. The chromone-3-carboxamides show high selectivity to hMAO-B, with compounds 9 and 12 displaying IC50 values at nanomolar range. (C) 2010 Published by Elsevier Ltd.
• An organocatalytic rearrangement of 2-(N-alkyl-/aryl-)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde
  作者：Sourav Maiti、Suman Kalyan Panja、Chandrakanta Bandyopadhyay

  DOI：10.1016/j.tetlet.2011.02.053

  日期：2011.4

  2-(Arylamino)-4-oxo-4H-1-benzopyran-3-carbaldehyde rearranges to 4-oxo-4H-1-benzopyran-3-carbanilide when treated with glycine in the presence of formalin, but under similar conditions 2-(alkylamino)-4-oxo-4H-1-benzopyran-3-carbaldehyde rearranges to 3-alkylaminomethylenechroman-2,4-dione. (C) 2011 Elsevier Ltd. All rights reserved.
• Discovery of New Chemical Entities for Old Targets: Insights on the Lead Optimization of Chromone-Based Monoamine Oxidase B (MAO-B) Inhibitors
  作者：Joana Reis、Fernando Cagide、Daniel Chavarria、Tiago Silva、Carlos Fernandes、Alexandra Gaspar、Eugenio Uriarte、Fernando Remião、Stefano Alcaro、Francesco Ortuso、Fernanda Borges

  DOI：10.1021/acs.jmedchem.6b00527

  日期：2016.6.23

  The discovery of new chemical entities endowed with potent, selective and reversible monoamine oxidase-B inhibitory activity is a clinically relevant subject. Therefore, a small library of chromone derivatives was synthesized and screened towards human monoamine oxidase isoforms (hMAO-A and hMAO-B). The structure-activity relationships studies strengthen the importance of the amide spacer and the direct

  具有有效的，选择性的和可逆的单胺氧化酶-B抑制活性的新化学实体的发现是临床相关主题。因此，合成了一个很小的色酮衍生物文库，并针对人单胺氧化酶同工型（hMAO-A和hMAO-B）进行了筛选。构效关系的研究加强了酰胺间隔基的重要性，以及羰基与γ-吡喃酮环的直接连接以及环外环中间位和对位取代基的存在。最有效的MAO-B抑制剂是N-（3'-氯苯基）-4-氧代-4H-色烯-3-羧酰胺（20）（IC50 = 403 pM）和N-（3'，4'-二甲基苯基）- 4-氧代-4H-色烯-3-羧酰胺（27）（IC50 = 669 pM），分别作为竞争性和非竞争性可逆抑制剂。计算对接研究提供了对酶-抑制剂相互作用的见解，并为观察到的选择性和效力提供了理论依据。化合物27因其良好的毒理学特性和理化特性而脱颖而出，该特性指向血脑屏障通透性，因此是随后进行动物研究的有效候选物。