4-[[4-(2-Methylbenzoyl)pyrimidin-2-yl]amino]benzonitrile | 1225464-96-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[[4-(2-Methylbenzoyl)pyrimidin-2-yl]amino]benzonitrile
• CAS: 1225464-96-9
• 化学式: C₁₉H₁₄N₄O
• 分子量: 314.346
• InChiKey: OLGHVEVIIORXJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  78.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[[4-(2-Methylbenzoyl)pyrimidin-2-yl]amino]benzonitrile 在 钾硼氢 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以84.6%的产率得到4-((4-(hydroxy(o-tolyl)methyl)pyrimidin-2-yl)amino)-benzonitrile
  参考文献：
  名称：

  Synthesis and structure–activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.07.023
• 作为产物：
  描述：

  4-N[2(4-氯吡啶基)]-氨基苯腈 在 氧气 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 4-[[4-(2-Methylbenzoyl)pyrimidin-2-yl]amino]benzonitrile
  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）。
• 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 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.