4-((4-((4-bromophenyl)(cyano)methyl)pyrimidin-2-yl)amino)benzonitrile | 1232684-01-3

• 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: 4-((4-((4-bromophenyl)(cyano)methyl)pyrimidin-2-yl)amino)benzonitrile
• CAS: 1232684-01-3
• 化学式: C₁₉H₁₂BrN₅
• 分子量: 390.242
• InChiKey: QDBDEFQIQSGBEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.51
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  85.39
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-((4-((4-bromophenyl)(cyano)methyl)pyrimidin-2-yl)amino)benzonitrile 在 air 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 4-((4-(1-(4-bromophenyl)-1-hydroxyethyl)pyrimidin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  CH（OH）-DAPYs的结构修饰作为新型HIV-1非核苷逆转录酶抑制剂

  摘要：

  合成了一系列在机翼I和中央嘧啶之间的CH（OH）接头处具有疏水基团的CR 2（OH）-二芳基嘧啶衍生物（CR 2（OH）-DAPYs），并评估了它们在MT-中的抗HIV活性4细胞培养。除化合物3k外，所有目标化合物均显示出对HIV-1野生型的抑制活性，EC 50值为7.21±1.99至0.067±0.006μM。其中，化合物3d显示出最有效的抗HIV-1活性（EC 50 = 0.067±0.006μM，SI> 592），在同一试验中，其效力比参考药物奈韦拉平（NVP）和德拉维定（DLV）高约2倍。此外，还研究了与HIV-1 RT的结合模式以及这些新衍生物的初步SAR研究。

  DOI：

  10.1016/j.bmc.2014.02.030
• 作为产物：
  描述：

  4-[(4-羟基-2-嘧啶基)氨基]苯腈 在 sodium hydride 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.5h， 生成 4-((4-((4-bromophenyl)(cyano)methyl)pyrimidin-2-yl)amino)benzonitrile
  参考文献：
  名称：

  CHX-DAPYs作为HIV-1非核苷类逆转录酶抑制剂的合成及生物学评价

  摘要：

  合成了一系列新的二芳基嘧啶（DAPYs），其特征是在机翼I和中央嘧啶环之间的亚甲基连接基上具有卤素原子，并评估了它们在MT-4细胞培养物中的抗HIV活性。两种最有希望的化合物7f和7g对野生型HIV-1表现出优异的活性，低纳摩尔EC 50值分别为0.005和0.009μM，与所有参比药物齐多夫定（AZT），拉米夫定相当或比其更有效（3TC），奈韦拉平（NEV），依非韦伦（EFV），德拉维定（DLV）和依曲韦林（ETV）。特别地，7g还对具有EC 50的双突变株103N + 181C表现出强大的活性。值为8.2μM。还研究了这一系列新的CHX-DAPYs的初步构效关系（SAR）和分子对接分析。

  DOI：

  10.1016/j.bmc.2014.03.020

文献信息

• Synthesis and Anti-HIV Activity of Aryl-2-[(4-cyanophenyl)amino]-4-pyrimidinone hydrazones as Potent Non-nucleoside Reverse Transcriptase Inhibitors
  作者：Xiao-Dong Ma、Shi-Qiong Yang、Shuang-Xi Gu、Qiu-Qin He、Fen-Er Chen、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1002/cmdc.201100334

  日期：2011.12.9

  A series of novel diarylpyrimidines (DAPYs) with a ketone hydrazone substituent on the methylene linker between the pyrimidine nucleus and the aryl moiety at the C‐4 position were synthesized, and their antiviral activity against human immunodeficiency virus (HIV)‐1 in MT‐4 cells was evaluated. Most compounds of this class exhibited excellent activity against wild‐type HIV‐1, with EC50 values in the

  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
• 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）。
• Design and synthesis of a new series of modified CH-diarylpyrimidines as drug-resistant HIV non-nucleoside reverse transcriptase inhibitors
  作者：Ge Meng、Yang Liu、Aqun Zheng、Fener Chen、Wenxue Chen、Erik De Clercq、Christophe Pannecouque、Jan Balzarini

  DOI：10.1016/j.ejmech.2014.05.059

  日期：2014.7

  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.
• 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.