2-(phenethylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile | 404910-67-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(phenethylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile
• 英文别名: 4-(4-methoxyphenyl)-6-oxo-2-phenethylsulfanyl-1H-pyrimidine-5-carbonitrile；4-(4-methoxyphenyl)-6-oxo-2-(2-phenylethylsulfanyl)-1H-pyrimidine-5-carbonitrile
• CAS: 404910-67-4
• 化学式: C₂₀H₁₇N₃O₂S
• 分子量: 363.44
• InChiKey: WNRAZCMIADPNKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  99.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  吗啉 、 2-(phenethylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以55%的产率得到4-(4-Methoxyphenyl)-6-morpholin-4-yl-2-(2-phenylethylsulfanyl)pyrimidine-5-carbonitrile
  参考文献：
  名称：

  Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in a Mixed Lymphocyte Reaction assay

  摘要：

  A series of novel pyrimidine analogues were synthesized and evaluated for immunosuppressive activity in the Mixed Lymphocyte Reaction assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. Systematic variation of the substituents at positions 2, 4 and 6 of the pyrimidine scaffold led to the discovery of 2-benzylthio-5-cyano-6-(4-methoxyphenyl)-4-morpholinopyrimidine with an IC50 value of 1.6 mu M in the MLR assay. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.032
• 作为产物：
  描述：

  4-甲氧基苯甲醛 在 哌啶 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 2-(phenethylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile
  参考文献：
  名称：

  Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in a Mixed Lymphocyte Reaction assay

  摘要：

  A series of novel pyrimidine analogues were synthesized and evaluated for immunosuppressive activity in the Mixed Lymphocyte Reaction assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. Systematic variation of the substituents at positions 2, 4 and 6 of the pyrimidine scaffold led to the discovery of 2-benzylthio-5-cyano-6-(4-methoxyphenyl)-4-morpholinopyrimidine with an IC50 value of 1.6 mu M in the MLR assay. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.032

文献信息

• Synthesis and Anti-HIV-1 Integrase Activitiy of Cyano Pyrimidinones
  作者：R. Ramajayam、Nilesh B. Mahera、Nouri Neamati、Mange Ram Yadav、Rajani Giridhar

  DOI：10.1002/ardp.200900066

  日期：2009.12

  6‐dihydropyrimidine‐5‐carbonitrile were synthesized and tested against recombinant HIV‐1 integrase in an enzyme assay. 2‐(Phenethylthio)‐4‐(4‐chlorophenyl)‐6‐oxo‐1,6‐dihydropyrimidine‐5‐carbonitrile 4m and 2‐(phenethylthio)‐4‐(3‐chlorophenyl)‐6‐oxo‐1,6‐dihydropyrimidine‐5‐carbonitrile 4o showed significant inhibition against integrase in the assay (strand transfer: IC50 values of 16 and 17 μM, respectively).

  合成了一系列 2-苯乙基/苄硫基-6-氧代-4-苯基-1,6-二氢嘧啶-5-甲腈，并在酶测定中针对重组 HIV-1 整合酶进行了测试。2-(苯乙硫基)-4-(4-氯苯基)-6-氧代-1,6-二氢嘧啶-5-甲腈4m和2-(苯乙硫基)-4-(3-氯苯基)-6-氧代-1,6 -dihydropyrimidine-5-carbonitrile 4o 在测定中显示出对整合酶的显着抑制（链转移：IC50 值分别为 16 和 17 μM）。
• [EN] COMPOSITIONS AND METHODS FOR INHIBITING N-SMASE2<br/>[FR] COMPOSITIONS ET PROCÉDÉS D'INHIBITION DE LA N-SMASE2
  申请人：UNIV CALIFORNIA

  公开号：WO2019055832A1

  公开（公告）日：2019-03-21

  Provided herein are compounds of Formula (I) and (II) and their salts, and compositions comprising such compounds that are useful for useful for modulating neutral sphingomyelinase 2 (n-SMase2) in cells. Also disclosed herein are methods of using the disclosed compounds and compositions for inhibiting the spread of Tau seeds from donor cells to recipient cells. Moreover, disclosed herein are methods of using the disclosed compounds and compositions for treating or preventing a neurodegenerative disorder, such as a tauopathy, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Lewy body dementia, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS).

  本文提供了化合物I和II及其盐，以及包含这些化合物的组合物，用于调节细胞中的中性鞘磷脂酰胆碱酰肌醇酶2（n-SMase2）。本文还披露了使用上述化合物和组合物抑制Tau种子从供体细胞传播到受体细胞的方法。此外，本文还披露了使用上述化合物和组合物治疗或预防神经退行性疾病的方法，例如tau病理、阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）、Lewy体痴呆、额颞叶痴呆和肌萎缩侧索硬化症（ALS）。
• Synthesis, docking studies, and evaluation of pyrimidines as inhibitors of SARS-CoV 3CL protease
  作者：R. Ramajayam、Kian-Pin Tan、Hun-Ge Liu、Po-Huang Liang

  DOI：10.1016/j.bmcl.2010.04.118

  日期：2010.6

  A series of 2-(benzylthio)-6-oxo-4-phenyl-1,6-dihydropyrimidine as SARS-CoV 3CL protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. Two candidates had encouraging results for the development of new anti-SARS compounds. (C) 2010 Elsevier Ltd. All rights reserved.
• COMPOSITIONS AND METHODS FOR INHIBITING N-SMASE2
  申请人：BILOUSOVA Tina

  公开号：US20200270216A1

  公开（公告）日：2020-08-27

  Provided herein are compounds of Formula (I) and (II) and their salts, and compositions comprising such compounds that are useful for useful for modulating neutral sphingomyelinase 2 (n-SMase2) in cells. Also disclosed herein are methods of using the disclosed compounds and compositions for inhibiting the spread of Tau seeds from donor cells to recipient cells. Moreover, disclosed herein are methods of using the disclosed compounds and compositions for treating or preventing a neurodegenerative disorder, such as a tauopathy, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Lewy body dementia, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS).
• Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in a Mixed Lymphocyte Reaction assay
  作者：Alessandro Stella、Kristien Van Belle、Steven De Jonghe、Thierry Louat、Jean Herman、Jef Rozenski、Mark Waer、Piet Herdewijn

  DOI：10.1016/j.bmc.2012.12.032

  日期：2013.3

  A series of novel pyrimidine analogues were synthesized and evaluated for immunosuppressive activity in the Mixed Lymphocyte Reaction assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. Systematic variation of the substituents at positions 2, 4 and 6 of the pyrimidine scaffold led to the discovery of 2-benzylthio-5-cyano-6-(4-methoxyphenyl)-4-morpholinopyrimidine with an IC50 value of 1.6 mu M in the MLR assay. (C) 2013 Elsevier Ltd. All rights reserved.