1,6-dihydro-6-oxo-4-phenyl-2-[(phenylmethyl)thio]-5-pyrimidinecarbonitrile

• 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: 1,6-dihydro-6-oxo-4-phenyl-2-[(phenylmethyl)thio]-5-pyrimidinecarbonitrile
• 英文别名: 2-(benzylthio)-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile；2-(benzylthio)-6-phenyl-3,4-dihydro-4-oxopyrimidine-5-carbonitrile；2-(benzylthio)-4-phenyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile；2-(Benzylsulfanyl)-4-hydroxy-6-phenyl-5-pyrimidinecarbonitrile；2-benzylsulfanyl-6-oxo-4-phenyl-1H-pyrimidine-5-carbonitrile
• 化学式: C₁₈H₁₃N₃OS
• 分子量: 319.387
• InChiKey: MNLIWUHXDSRCED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,6-dihydro-6-oxo-4-phenyl-2-[(phenylmethyl)thio]-5-pyrimidinecarbonitrile 在 三氯氧磷 作用下， 以 1,4-二氧六环 、 异丙醇 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and cytotoxic activity of novel 4-amino-5-cyano-2-sulfonylpyrimidines

  摘要：

  Novel 4-amino-5-cyano-2-sulfonylpyrimidines were prepared based on three-component cyclization between isothiouronium salts, benzaldehydes and malononitrile, followed by oxidation of the sulfide moiety with Oxone. The cytotoxic activity of the synthesized compounds, as well as the induction of apoptosis, inhibition of the cell cycle and proliferation tests were performed on selected cancer cell lines A431, A549, A375, HCT 116, MCF7, LNCap and SH-SY5Y.

  DOI：

  10.1016/j.mencom.2020.09.017
• 作为产物：
  描述：

  1,2,3,4-四氢-4-氧代-6-苯基-2-硫代-5-嘧啶甲腈 生成 1,6-dihydro-6-oxo-4-phenyl-2-[(phenylmethyl)thio]-5-pyrimidinecarbonitrile
  参考文献：
  名称：

  KHALII, ZARIF HALLEM;HAFEZ, ALI AHMED ABDEL;AHMED, AHMED ABDO, PHOSPH. SULFUR AND SILICON AND RELAT. ELEM., 45,(1989) N-2, C. 81-93

  摘要：

  DOI：

文献信息

• An efficient and facile synthesis of inhibitors for hepatitis C viral and anti-SARS agents: 4-aryl-5-cyano-1,6-dihydro-2-thiouracils
  作者：Liangce Rong、Shan Yin、Sheng Xia、Shimin Tao、Yanhui Shi、Shujiang Tu

  DOI：10.1007/s11164-011-0434-4

  日期：2012.3

  One-pot, multicomponent reaction for the synthesis of 4-aryl-5-cyano-1,6-dihydro-2-thiouracils via three-component from aromatic aldehydes, ethyl 2-cyanoacetate and S-benzylisothiourea hydrochloride (methyl carbamimidothioate sulfate) under methanol is described. These compounds have many drug activities, such as anti-hepatitis C viral, anti-Severe acute respiratory syndrome and anti-HIV-1 integrese activity. The advantages of this procedure include the short reaction time, mild reaction conditions and excellent yields.

  描述了一种一锅法多组分反应，通过芳香醛、乙基2-氰基乙酸酯和盐酸硫代脲苄基（甲基氨基硫酸酯）在甲醇中合成4-芳基-5-氰基-1,6-二氢-2-硫脲嘧啶的三组分反应。这些化合物具有多种药物活性，如抗丙型肝炎病毒、抗严重急性呼吸综合症和抗HIV-1整合酶活性。这种方法的优点包括反应时间短、反应条件温和和产率优秀。
• 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）。
• α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide (NAD⁺) Biosynthesis
  作者：Roberto Pellicciari、Paride Liscio、Nicola Giacchè、Francesca De Franco、Andrea Carotti、Janet Robertson、Lucia Cialabrini、Elena Katsyuba、Nadia Raffaelli、Johan Auwerx

  DOI：10.1021/acs.jmedchem.7b01254

  日期：2018.2.8

  NAD(+) has a central function in linking cellular metabolism to major cell-signaling and gene-regulation pathways. Defects in NAD(+) homeostasis underpin a wide range of diseases, including cancer, metabolic disorders, and aging. Although the beneficial effects of boosting NAD(+) on mitochondrial fitness, metabolism, and lifespan are well established, to date, no therapeutic enhancers of 4 novo NAD(+) biosynthesis have been reported. Herein we report the discovery of 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thieny1)-2-pyrimidinyl]thio]methyl]phenylacetic acid (TES-1025, 22), the first potent and selective inhibitor of human ACMSD (IC50 = 0.013 mu M) that increases NAD(+) levels in cellular systems. The results of physicochemical-property, ADME, and safety profiling, coupled with in vivo target-engagement studies, support the hypothesis that ACMSD inhibition increases de novo NAD(+) biosynthesis and position 22 as a first-class molecule for the evaluation of the therapeutic potential of ACMSD inhibition in treating disorders with perturbed NAV-supply or homeostasis.
• 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.
• Synthesis of novel 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles as potential antimicrobial agents
  作者：Ebtehal S. Al-Abdullah、Abdul-Rahman M. Al-Obaid、Omar A. Al-Deeb、Elsayed E. Habib、Ali A. El-Emam

  DOI：10.1016/j.ejmech.2011.08.003

  日期：2011.9

  New series of 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles namely, 2-substitued thio-6-phenyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles (5a-d, 6, 7a-d, 8), 2-(4-chlorobenzylthio)-4-chloro-6-phenylpyrimidine-5-carbonitrile (9), 2-(4-chlorobenzylthio)-4-arylthio-6-phenylpyrimidine-5-carbonitriles (10a-d) and 2-(4-chlorobenzylthio)-4-arylamino-6-phenylpyrimidine-5-carbonitriles (11a-d) was synthesized and tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 5b, 5c, 6, 7a, 7b, 7c, 9 and 11a displayed marked antibacterial activity particularly against the tested Gram-positive bacteria, while compounds 6, 7c, 7d and 9 were moderately or weakly active against C. albicans. (C) 2011 Elsevier Masson SAS. All rights reserved.