3-amino-4-cyano-1-(4-methoxyphenyl)-1H-2-pyrrolecarboxylic acid ethyl ester | 145162-32-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-amino-4-cyano-1-(4-methoxyphenyl)-1H-2-pyrrolecarboxylic acid ethyl ester
• 英文别名: 3-amino-4-cyan-1-p-anisyl-pyrrol-2-carbonsaeureethylester；Ethyl 3-amino-4-cyano-1-(4-methoxyphenyl)pyrrole-2-carboxylate
• CAS: 145162-32-9
• 化学式: C₁₅H₁₅N₃O₃
• 分子量: 285.302
• InChiKey: OAZKRUFRWRUYDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  90.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-amino-4-cyano-1-(4-methoxyphenyl)-1H-2-pyrrolecarboxylic acid ethyl ester 在 乙醇 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.5h， 生成 [7-cyano-5-(4-methoxyphenyl)-4-oxo-3,4-dihydropyrrolo[3,2-d]pyrimidin-2-ylsulfanyl]acetic acid ethyl ester
  参考文献：
  名称：

  New Syntheses of 2-Alkylthio-4-oxo-3,4-dihydroquinazolines, 2 - Alkylthio - quinazolines, as well as Their Hetero Analogues

  摘要：

  N-Chloroacetylanthranilic acid ethyl ester reacts with potassium thiocyanate in the presence of alcohol to give the (4-oxo-3,4-dihydroquinazolin-2-yl-sulfanyl)acetic acid ester (3a). In the presence of water or amines the acetic acid derivative (3b) or the acetamide derivatives (3c,d) are obtained. 2-Amino-di-oxo-3,4-dihydroquinazolines (4) arise if vigorous reaction conditions are employed. Analogously, N-chloroacetyl derivatives of 5-membered heterocycles with enaminocarbonyl structure (5, 7, 9, 11, 13, 20, 23) react with potassium thiocyanate to yield thieno[2,3-d]-, thieno[3,2-d]-, imidazo[4,5-d]-, pyrrolo[3,2-d]-, and thiazolo[4,5-d]pyrimidines (6, 8, 10, 12, 14, 21, 24). Quinazolines (18, 19) are formed from the reaction of 2-chloroacetylaminoacetophenone (16a) and 2-chloroacetylaminobenzophenone (16b) with potassium thiocyanate and subsequent treatment of the intermediates with. amines.

  DOI：

  10.3987/com-00-8954
• 作为产物：
  描述：

  甲氧苯胺 在 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 3-amino-4-cyano-1-(4-methoxyphenyl)-1H-2-pyrrolecarboxylic acid ethyl ester
  参考文献：
  名称：

  作为新型 FXa 抑制剂的吡咯并 [3,2-d] 嘧啶酮衍生物的合成

  摘要：

  已设计并合成了一系列吡咯并[3,2- d ]嘧啶酮化合物作为新型 FXa 抑制剂。受试化合物的生物测定显示出中等至极好的体外抗凝血效力。进一步在大鼠，FeCl 3诱导的静脉血栓形成模型中评估FXa抑制和生物活性，表明化合物17a具有良好的FXa抑制活性（IC 50 = 1.57 nM）和体内抗血栓效力。化合物17a的抗凝血作用在体外或体内均呈剂量依赖性. 结果进一步证实了我们的假设，即大共轭结构是理想的骨架结合 FXa。

  DOI：

  10.1016/j.bmcl.2023.129127

文献信息

• Synthesis, biological evaluation, and molecular modeling of nitrile‐containing compounds: Exploring multiple activities as anti‐Alzheimer agents
  作者：Daniel Silva、Eduarda Mendes、Eleanor J. Summers、Ana Neca、Ana C. Jacinto、Telma Reis、Paula Agostinho、Irene Bolea、M. Luisa Jimeno、M. Luisa Mateus、Ana M. F. Oliveira‐Campos、Mercedes Unzeta、José Marco‐Contelles、Magdalena Majekova、Rona R. Ramsay、M. Carmo Carreiras

  DOI：10.1002/ddr.21594

  日期：2020.4

  the best lead for trifunctional inhibition against MAO A (0.34 μM), MAO B (0.26 μM), and AChE (52 μM), while 32 exhibited a lead for selective MAO A (0.12 μM) inhibition coupled to AChE (48 μM) inhibition. Computational analysis revealed that the malononitrile group can find an advantageous position with the aromatic cleft and FAD of MAO A or MAO B. However, the total binding energy can be handicapped

  基于具有腈基的氨基杂环的单胺氧化酶（MAO）抑制特性，我们进行了系统的探索，以发现具有双重MAO和AChE抑制活性以及Aβ抗聚集特性的新型腈。合成并评估了83种含腈化合物，其中13种是新化合物。体外筛选显示，一种新化合物31对MAO A（0.34μM），MAO B（0.26μM）和AChE（52μM）的三功能抑制作用表现出最好的铅，而32表现出选择性MAO A（0.12μM）抑制与AChE（48μM）抑制耦合的先导。计算分析表明，丙二腈基团可以在MAO A或MAO B的芳族裂隙和FAD上找到有利的位置。但是，总的结合能可能会因配体分子扭曲和随后的破坏而造成的内部损失而受阻。共轭（MAO B中的32与共轭31相比）。共轭对于AChE以及丙二腈的亲水特性也很重要，丙二腈使该基团与水性环境紧密接触，见83。尽管31和32对Aβ1–42有影响该化合物非常弱，对63和65以及对新化合物75的影响表明
• Synthesis of New Tacrine Analogues from 4-Amino-1<i>H</i>-pyrrole-3-carbonitrile
  作者：Abdellatif M. Salaheldin、Ana M. F. Oliveira-Campos、Pier Parpot、Lígia M. Rodrigues、M. Manuel Oliveira、Francisco P. Feixoto

  DOI：10.1002/hlca.200900190

  日期：2010.2

  preparation of 4‐amino‐1H‐pyrrole‐3‐carbonitrile derivatives and their transformation into new substituted pyrrolo[3,2‐b]pyridines is described. The one‐step transformation was carried out via Friedländer reaction under microwave irradiation and by classical heating methods. The use of microwave irradiation led to high conversion and shorter reaction times.

  描述了一种简单的制备4-氨基-1 H-吡咯-3-腈衍生物并将其转化为新的取代吡咯并[3,2- b ]吡啶的方法。一步转化是在微波辐射下通过Friedländer反应并通过经典的加热方法进行的。微波辐射的使用导致高转化率和较短的反应时间。
• 吡咯并嘧啶酮类衍生物及其制备方法和应用
  申请人：南京中瑞药业有限公司

  公开号：CN115073470A

  公开（公告）日：2022-09-20

  本发明公开了结构如式Ⅰ所示的吡咯并嘧啶酮类衍生物，其中，R1选自C1‑C3烷氧基、卤素、氰基，n＝1、2；R2选自氰基、甲酰胺基；R3选自通过凝血酶原时间(PT)试验以及FXa体外抑制试验、大鼠体内抗血栓形成试验、抗凝血活性实验表明所述的吡咯并嘧啶酮类衍生物具有显著的抗凝血作用。因此，本发明还公开了所述的吡咯并嘧啶酮类衍生物在制备血液抗凝剂中的应用，所述的血液抗凝剂为Xa因子抑制剂。
• Zur Synthese von 3-Amino-pyrrolen durch Thorpe-Ziegler-Cyclisierung
  作者：K. Gewald、H. Sch�fer、P. Bellmann、U. Hain

  DOI：10.1002/prac.19923340608

  日期：——

  N-Aryl and alkylaminomethylene cyanacetic acid derivatives 1 react with alpha-halogencarbonyl compounds 2 in the presence of potassium carbonate/sodium ethoxide to yield the substituted 3-amino-pyrroles 6. Using the same principle of cyclization pyrrole derivatives 6 can also be obtained by reaction of beta-chloro- and beta-alkoxymethylenemalononitriles 4 with beta-aminocarbonyl compounds 5. From the malononitrile derivatives 1 containing the methylthio group in the beta-position, and alpha-halogen ketones 7, the 2-dicyanomethylene oxazolines 8 arise which undergo alkoholysis by treatment with sodium alkoxide to form the 3-amino-5-alkoxy-pyrrole derivatives 9.
• New Syntheses of 2-Alkylthio-4-oxo-3,4-dihydroquinazolines, 2 - Alkylthio - quinazolines, as well as Their Hetero Analogues
  作者：Margit Gruner、Matthias Rehwald、Katrin Eckert、Karl Gewald

  DOI：10.3987/com-00-8954

  日期：——

  N-Chloroacetylanthranilic acid ethyl ester reacts with potassium thiocyanate in the presence of alcohol to give the (4-oxo-3,4-dihydroquinazolin-2-yl-sulfanyl)acetic acid ester (3a). In the presence of water or amines the acetic acid derivative (3b) or the acetamide derivatives (3c,d) are obtained. 2-Amino-di-oxo-3,4-dihydroquinazolines (4) arise if vigorous reaction conditions are employed. Analogously, N-chloroacetyl derivatives of 5-membered heterocycles with enaminocarbonyl structure (5, 7, 9, 11, 13, 20, 23) react with potassium thiocyanate to yield thieno[2,3-d]-, thieno[3,2-d]-, imidazo[4,5-d]-, pyrrolo[3,2-d]-, and thiazolo[4,5-d]pyrimidines (6, 8, 10, 12, 14, 21, 24). Quinazolines (18, 19) are formed from the reaction of 2-chloroacetylaminoacetophenone (16a) and 2-chloroacetylaminobenzophenone (16b) with potassium thiocyanate and subsequent treatment of the intermediates with. amines.