N-(2-甲酰基-3-甲氧基苯基)-2,2-二甲基丙酰胺 | 82673-65-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(2-甲酰基-3-甲氧基苯基)-2,2-二甲基丙酰胺
• 英文名称: N-(2-formyl-3-methoxyphenyl)pivalamide
• 英文别名: 2-formyl-3-methoxy-N-pivaloylaniline；N-(2-formyl-3-methoxyphenyl)-2,2-dimethylpropanamide
• CAS: 82673-65-2
• 化学式: C₁₃H₁₇NO₃
• 分子量: 235.283
• InChiKey: YXASJBNPUMOCRO-UHFFFAOYSA-N

物化性质

• 熔点：
  82-84°
• 沸点：
  416.7±35.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  N-(2-甲酰基-3-甲氧基苯基)-2,2-二甲基丙酰胺 在 盐酸 、 氢溴酸 、 potassium carbonate 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 3-(methylcarbamoyl)quinolin-5-yl dimethylcarbamate
  参考文献：
  名称：

  Rational design of carbamate-based dual binding site and central AChE inhibitors by a “biooxidisable” prodrug approach: Synthesis, in vitro evaluation and docking studies

  摘要：

  Herein, we report a new class of dual binding site AChE inhibitor 4 designed to exert a central cholinergic activation thanks to a redox-activation step of a prodrug precursor 3. Starting from potent pseudo irreversible quinolinium salts AChE inhibitors 2 previously reported, a new set of diversely substituted quinolinium salts 2a-p was prepared and assayed for their inhibitory activity against AChE. Structure activity relationship (SAR) analysis of 2a-p coupled with molecular docking studies allowed us to determine which position of the quinolinium scaffold may be considered to anchor the phtalimide fragment presumed to interact with the peripheral anionic site (PAS). In addition, molecular docking provided insight on the linker length required to connect both quinolinium and phatlimide moieties without disrupting the crucial role of quinolinium salt moiety within the catalytic active site (CAS); namely placing the carbamate in the correct position to trigger carbamylation of the active-site serine hydroxyl. Based on this rational design, the putative dual binding site inhibitor 4 and its prodrug 3 were synthesized and subsequently evaluated in vitro against AChE. Pleasingly, whereas compound 4 showed to be a highly potent inhibitor of AChE (IC50 = 6 nM) and binds to AChE-PAS to the same extent as donepezil, its prodrug 3 revealed to be inactive (IC50> 10 mu M). These preliminary results constitute one of the few examples of carbamate-based dual binding site AChE inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.05.057
• 作为产物：
  描述：

  N,N-二甲基甲酰胺 在 正丁基锂 、 氯化铵 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以65%的产率得到N-(2-甲酰基-3-甲氧基苯基)-2,2-二甲基丙酰胺
  参考文献：
  名称：

  [EN] BENZOXAZINONE DERIVATIVES, PREPARATION THEREOF AND USES IN THE TREATMENT OF CNS AND OTHER DISORDERS
  [FR] DERIVES DE BENZOXAZINONE, PREPARATION DE CEUX-CI ET UTILISATIONS DE CEUX-CI DANS LE TRAITEMENT DE TROUBLES DU SNC ET D'AUTRES TROUBLES

  摘要：

  公开了化合物的公式(I)及其药用盐：其中A、R1、R2、R3、p、q、A和X的定义如规范中所述。还公开了化合物的制备方法以及在治疗中枢神经系统和其他疾病，包括抑郁症和焦虑症中的用途。

  公开号：

  WO2004046124A1

文献信息

• New Enzyme Models of Chloroperoxidase: Improved stability and catalytic efficiency of iron porphyrinates containing a thiolato ligand
  作者：Hans-Achim Wagenknecht、C�cile Claude、Wolf-Dietrich Woggon

  DOI：10.1002/hlca.19980810554

  日期：——

  The heme-thiolate protein chloroperoxidase (CPO) catalyzes the chlorination of activated CH bonds. A reaction mechanism is proposed for this enzymatic transformation (Scheme 1), and a new iron(III) porphyrinate complex 13 is synthesized containing pentafluorophenyl groups at two meso-positions and a thiophenolato ligand coordinating to the Fe-atom (Schemes 2 and 3). Due to the presence of the electron-withdrawing

  血红素硫醇盐蛋白氯过氧化物酶（CPO）催化活化的CH键的氯化。提出了用于该酶促转化的反应机理（方案1），并且合成了新的卟啉铁（III）配合物13，其在两个内位含有五氟苯基基团和与Fe原子配位的硫代酚基配体（方案2和3）。 。由于该吸电子取代基的存在下，催化剂13是氧化剂（次氯酸）和chlorinates，明显抗性例如，一氯（5）中，用转换数高达1530的氧化还原电位13，È0 =-134 mV，还原态13的CO加合物的Soret带（λmax 448 nm）接近酶CPO的相应值。
• [EN] QUINOLONES AS INHIBITORS OF CLASS IV BROMODOMAIN PROTEINS<br/>[FR] QUINOLONES À TITRE D'INHIBITEURS DE PROTÉINES À BROMODOMAINES DE CLASSE IV
  申请人：UCL BUSINESS PLC

  公开号：WO2016034512A1

  公开（公告）日：2016-03-10

  The present invention provides compounds of formula (I) as described herein and pharmaceutically acceptable salts, hydrates and solvates thereof for use in medicine, for example in the treatment of acute myeloid leukaemia:

  本发明提供了如下所述的化合物(I)及其药用可接受的盐、水合物和溶剂合物，用于医学上的应用，例如用于治疗急性髓样白血病：
• Benzoxazinone derivatives, preparation thereof and uses in the treatment of cns and other disorders
  申请人：Bertani Barbara

  公开号：US20060264429A1

  公开（公告）日：2006-11-23

  Compounds of formula (I) and pharmaceutically acceptable salts thereof are disclosed: wherein A, R1, R2, R3, p, q, A and X are as defined in the specification. Preparation of the compounds and uses in the treatment of CNS and other disorders, including depression and anxiety, are also disclosed.

  公开了化学式（I）的化合物及其药学上可接受的盐：其中A、R1、R2、R3、p、q、A和X的定义如规范中所述。还公开了这些化合物的制备方法以及在治疗中枢神经系统和其他疾病，包括抑郁和焦虑症方面的用途。
• BENZOXAZINONE DERIVATIVES, PREPARATION THEREOF AND USES IN THE TREATMENT OF CNS AND OTHER DISORDERS
  申请人：Bertani Barbara

  公开号：US20090076274A1

  公开（公告）日：2009-03-19

  Intermediates useful in the preparation of compounds of formula (I) and pharmaceutically acceptable salts thereof are disclosed: wherein A, R1, R2, R3, , p, q, and X are as defined in the specification.

  本文披露了在制备式(I)化合物及其药学上可接受的盐中有用的中间体：其中A、R1、R2、R3、p、q和X如规范中所定义。
• 10.1039/d4ob00649f
  作者：Bettoni, Léo、Joly, Nicolas、Mendas, Inès、Moscogiuri, Matteo Maria、Lohier, Jean-François、Gaillard, Sylvain、Poater, Albert、Renaud, Jean-Luc

  DOI：10.1039/d4ob00649f

  日期：——

  Here we report an iron-complex-catalyzed synthesis of various mono- and di-substituted quinolin-2(1H)-ones achieved via the intramolecular acceptorless dehydrogenative cyclization of amido-alcohols. This approach for the synthesis of N-heterocycles has provided access to underdescribed disubstituted quinolinones and represents an alternative to the well-known palladium-catalyzed coupling reactions

  在这里，我们报道了通过酰胺醇的分子内无受体脱氢环化实现的各种单取代和双取代的喹啉-2(1 H )-酮的铁络合物催化合成。这种合成 N-杂环的方法提供了获得未描述的二取代喹啉酮的途径，并且代表了众所周知的钯催化偶联反应的替代方案。