2-(4-cyanophenylamino)-4-(2-chlorobenzoyl)pyrimidine | 1225464-84-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(4-cyanophenylamino)-4-(2-chlorobenzoyl)pyrimidine
• CAS: 1225464-84-5
• 化学式: C₁₈H₁₁ClN₄O
• 分子量: 334.765
• InChiKey: DTQASWWSXHMVGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.67
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-(4-cyanophenylamino)-4-(2-chlorobenzoyl)pyrimidine 在 sodium cyanoborohydride 、 溶剂黄146 、 sodium sulfate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 2-(4-cyanophenylamino)-4-(2-chlorophenyl-N-methylaminomethyl)pyrimidine
  参考文献：
  名称：

  Design and synthesis of a new series of modified CH-diarylpyrimidines as drug-resistant HIV non-nucleoside reverse transcriptase inhibitors

  摘要：

  This article reports the design, synthesis and antiviral evaluation of a new series of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The basic skeleton of these target 18 molecules is diarylpyrimidine featuring a substituted amino group between the pyrimidine scaffold and the aryl wing. All of the new compounds have been characterized by spectra analysis. The entire target molecules were evaluated for their in vitro anti-HIV activity with controlling group of FDA approved drugs. Most of them showed good to potent activities against wild-type (WT) HIV-1 with IC50 values in the range of 0.0175-69.21 mu M. 2-(4-Cyanophenylamino)-4-(2-cyanovinylphenylhydrazonomethyl)pyrimidine (1d) displayed potent anti-HIV-1 activity against WT HIV-1 with a selectivity index (SI) of 106367 and an IC50 value of 1.75 nM, which was 47 fold lower than that of AZT. Compound Id also showed a broad-spectrum inhibitory activity, with an IC50 value of 5.33 mu M and 5.05 mu M against both HIV-1 double-mutated (K103N/Y181C) strain and HIV-2 strain, respectively. The preliminary structure activity relationship (SAR) was also investigated. The binding modes with HIV-1 RT for both the wild type and mutant type have also been discussed. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.059
• 作为产物：
  描述：

  邻氯苯乙腈 在 氧气 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 2-(4-cyanophenylamino)-4-(2-chlorobenzoyl)pyrimidine
  参考文献：
  名称：

  芳基-2-[（4-氰基苯基）氨基] -4-嘧啶酮的合成及其抗HIV活性作为有效的非核苷类逆转录酶抑制剂

  摘要：

  合成了一系列新颖的二芳基嘧啶（DAPYs），其在嘧啶核和C-4位置的芳基部分之间的亚甲基连接基上具有取代基，并在MT‐中具有抗人免疫缺陷病毒（HIV）-1的抗病毒活性。评价了4个细胞。大多数此类化合物对野生型HIV-1表现出优异的活性，EC 50值在1.7-13.2 n M的范围内。在这些化合物中，2-溴苯基-2-[[（4-氰基苯基）氨基] -4-嘧啶酮（9 k）显示出最有效的抗HIV-1活性（EC 50 = 1.7±0.6 n M），具有优异的抗HIV-1活性。对未感染细胞的选择性（SI = 5762）。此外，4-甲基苯基类似物9 d（EC 50 = 2.4±0.2N的中号，SI = 18461）显示广谱HIV的抑制活性，用EC 50个的2.4±0.2 n个值中号μ对野生型HIV-1，5.3±0.4中号抗HIV-1双突变菌株RES056（K103N + Y181C），和5.5μ中号抗HIV-2

  DOI：

  10.1002/cmdc.201100334

文献信息

• Synthesis and biological evaluation of 4-(hydroxyimino)arylmethyl diarylpyrimidine analogues as potential non-nucleoside reverse transcriptase inhibitors against HIV
  作者：Xiao-Qing Feng、Zhao-Sen Zeng、Yong-Hong Liang、Fen-Er Chen、Christophe Pannecouque、Jan Balzarini、Erik De Clercq

  DOI：10.1016/j.bmc.2010.03.007

  日期：2010.4

  pyrimidine scaffold and the aryl wing I have been synthesized and tested in MT-4 cells culture as non-nucleoside reverse transcriptase inhibitors against human immunodeficiency virus (HIV). Most of these new congeners exhibited moderate to excellent activity against wild-type virus with an EC50 value ranging from 0.569 μM to 0.005 μM. 4-(4-((Hydroxyimino) (3-methoxyphenyl)methyl)pyrimidin-2-ylamino)benzonitrile

  已经合成了一系列新颖的在嘧啶支架和芳基翼I之间具有羟基亚氨基甲基的二芳基嘧啶类似物，并已在MT-4细胞培养中作为抗人免疫缺陷病毒（HIV）的非核苷逆转录酶抑制剂进行了测试。这些新同源物中的大多数对野生型病毒表现出中等至出色的活性，EC 50值为0.569μM至0.005μM。4-（4-（（（羟基亚氨基）（3-甲氧基苯基）甲基）嘧啶-2-基氨基）苯甲腈（12n）被确定为该新系列中活性最高的化合物（EC 50  = 0.025μM，SI> 1223）与对HIV-1双突变株（K103N + Y181C）具有中等活性（EC 50 除具有抗HIV-2活性外，其EC 50值为8.31μM（= 8.72μM）。还研究了新合成的DAPY之间的初步构效关系（SAR）。
• 含取代芳基脲亚胺基二芳基嘧啶类衍生物及其制备方法和用途
  申请人：复旦大学

  公开号：CN114539162B

  公开（公告）日：2023-05-30

  本发明属于医药技术领域，具体为一种含取代芳基脲亚胺基二芳基嘧啶类衍生物及其制备方法和用途。本发明的化合物结构如通式ZFI所示，还包含其药用盐，水合物及溶剂化物，其多晶或共晶，其同样生物功能的前体和衍生物。体外酶水平的对抗PARP‑1活性评价实验结果显示，该类小分子中具有与PARP‑1结合迥异的结构特征，并从蛋白质晶体结构与药物相互作用特征上进行了分析，阐明分子结构特征的依据。该类化合物具有潜在治疗与调节和PARP‑1表达异常相关性疾病(如肿瘤)的生物活性，且具有较低细胞毒性，可用于制备与PARP‑1表达异常相关的肿瘤等疾病治疗药物。
• 一种HIV-1逆转录酶抑制剂及其合成方法
  申请人：复旦大学

  公开号：CN114539163B

  公开（公告）日：2023-05-30

  本发明属于医药技术领域，具体为一种HIV‑1逆转录酶抑制剂及其合成方法。本发明的HIV‑1逆转录酶抑制剂为取代芳基脲亚胺基二芳基嘧啶类衍生物，还包含其药用盐，水合物及溶剂化物，其多晶或共晶，其同样生物功能的前体和衍生物。从体外细胞水平的抗HIV‑1活性实验结果显示，该类化合物具有较强的抗HIV‑1生物活性，可显着抑制HIV‑1病毒感染的MT‑4细胞内病毒复制，并且具有较低的细胞毒性和较好的选择性。本发明还包括此类化合物的组合物在治疗艾滋病等相关药物中的应用。
• Synthesis and structure–activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs
  作者：Shuang-Xi Gu、Qiu-Qin He、Shi-Qiong Yang、Xiao-Dong Ma、Fen-Er Chen、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1016/j.bmc.2011.07.023

  日期：2011.9

  A series of 26 diarylpyrimidines, characterized by the hydroxymethyl linker between the left wing benzene ring and the central pyrimidine, were synthesized and evaluated for in vitro anti-HIV activity. Most of the compounds exhibited moderate to excellent activities against wild-type HIV-1. Among them, compound 10i, bearing a chlorine atom at the C-2 position of left benzene ring, was the best congener and showed potent activity against wild-type HIV-1 with an EC50 value of 0.009 mu M, along with moderate activities against the double RT mutant (K103N + Y181C) HIV-1(IIIB) and HIV-2(ROD) with an EC50 value of 6.2 and 6.0 mu M, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated. (C) 2011 Elsevier Ltd. All rights reserved.
• Design and synthesis of a new series of cyclopropylamino-linking diarylpyrimidines as HIV non-nucleoside reverse transcriptase inhibitors
  作者：Yang Liu、Ge Meng、Aqun Zheng、Fener Chen、Wenxue Chen、Erik De Clercq、Christophe Pannecouque、Jan Balzarini

  DOI：10.1016/j.ejps.2014.06.003

  日期：2014.10

  A new series of 29 diarylpyrimidine analogues featuring a cyclopropylamino group between the pyrimidine scaffold and the aryl wing have been synthesized. All of the new compounds have been characterized by spectra analysis. The target molecules were evaluated for their in vitro anti-HIV activity with FDA-approved drugs as references. Some of the compounds exhibited moderate to potent activities against wild-type HIV-1. The compound 4-((4-((cyclopropylamino)(2,5-difluorophenyl)methyl)pyrimidin-2-yl)amino)benzonitrile (1e) displayed potent anti-HIV-1 activity against WT HIV-1 with an IC50 of 0.099 μM and a selectivity index of 2302. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated.