4-甲基硫代-6-氧代-1,6-二氢嘧啶-5-甲腈 | 16071-28-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 4-甲基硫代-6-氧代-1,6-二氢嘧啶-5-甲腈
• 英文名称: 3,4-dihydro-4-oxo-6-(methylthio)-5-pyrimidinecarbonitrile
• 英文别名: 6-methylthiouracil-5-carbonitrile；4-(methylthio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile；3,4-dihydro-6-methymercapto-4-oxopyrimidine-5-carbonitrile；4-methylsulfanyl-6-oxo-1H-pyrimidine-5-carbonitrile
• CAS: 16071-28-6
• 化学式: C₆H₅N₃OS
• mdl: MFCD08234545
• 分子量: 167.191
• InChiKey: XYTYZNCJKPMHEX-UHFFFAOYSA-N

物化性质

• 沸点：
  251.6±50.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  4-甲基硫代-6-氧代-1,6-二氢嘧啶-5-甲腈 在 Oxone 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.08h， 生成 3-(5-cyano-6-(methylsulfonyl)pyrimidin-4-ylamino)-N-methoxy-4-methylbenzamide
  参考文献：
  名称：

  5-Cyanopyrimidine Derivatives as a Novel Class of Potent, Selective, and Orally Active Inhibitors of p38α MAP Kinase

  摘要：

  A novel class of 5-cyanopyrimidine-based inhibitors of p38 alpha MAP kinase has been investigated. Analogues optimized through SAR iterations display low nanomolar enzymatic and cellular activity. The in vivo efficacy of this class of p38 inhibitors was demonstrated by 3a and 3b (> 50% reduction in TNF levels when orally dosed at 5 mg/kg, 5 h prior to LPS administration in an acute murine model of inflammation). For 3a and 3b, the previously identified N-methoxybenzamide moiety (1) was replaced with N-(isoxazol-3-yl)benzamide, thereby providing increased metabolic stability. Cyanopyrimidine 3a demonstrated 100% oral bioavailability in mouse. High p38 kinase selectivity versus over 20 kinases was observed for analogue 3b. Direct hydrogen bonding of the cyano nitrogen of the 5-cyanopyrimidine core to the backbone NH of Met109 was confirmed by X-ray crystallographic analysis of 3a bound to p38 alpha.

  DOI：

  10.1021/jm0503594
• 作为产物：
  描述：

  3,3-双(甲硫基)-2-氰基丙烯酸乙酯 、 甲脒 以 乙醇 为溶剂， 生成 4-甲基硫代-6-氧代-1,6-二氢嘧啶-5-甲腈
  参考文献：
  名称：

  Suitably functionalised pyrimidines as potential antimycotic agents

  摘要：

  Various suitably functionalised pyrimidine derivatives have been synthesized to explore their potential as antimycotic agents. Some of the synthesized compounds 4c, 4d, 8a-e have shown highly significant in vitro antifungal activity against five human pathogenic fungi. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00091-3

文献信息

• Efficient One‐Step Synthesis of a Key Intermediate for the Synthesis of Azole Antifungals Using the Mitsunobu Protocol
  作者：Jitendra A. Sattigeri、Jasbir S. Arora、Ashwani K. Verma、Sanjay Malhotra、Mohammad Salman

  DOI：10.1080/00397910500297461

  日期：2005.11

  single‐step process for coupling (2R,1S)‐1‐[2‐(2,4‐difluorophenyl)‐2‐oxiranyl]ethanol and various 1,2,4‐triazolones utilizing the Mitsunobu protocol is described. The product so formed is a key intermediate in the synthesis of azole antifungals with potent and broad‐spectrum activity against yeast and filamentous fungi.

  摘要描述了使用 Mitsunobu 协议偶联 (2R,1S)-1-[2-(2,4-二氟苯基)-2-环氧乙烷基]乙醇和各种 1,2,4-三唑酮的简单单步过程。如此形成的产物是合成唑类抗真菌剂的关键中间体，对酵母和丝状真菌具有强效和广谱活性。
• Kohra, Shinya; Tominaga, Yoshinori; Hosomi, Akira, Journal of Heterocyclic Chemistry, 1988, vol. 25, p. 959 - 968
  作者：Kohra, Shinya、Tominaga, Yoshinori、Hosomi, Akira

  DOI：——

  日期：——
• Ram, Vishnu J; Haque, Navedul; Nath, Mahendra, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1993, vol. 32, # 7, p. 754 - 759
  作者：Ram, Vishnu J、Haque, Navedul、Nath, Mahendra

  DOI：——

  日期：——
• Cardiotonic agents. 5. Fragments from the heterocycle-phenyl-imidazole pharmacophore
  作者：Paul W. Erhardt、Alfred A. Hagedorn、David Davey、Cynthia A. Pease、Bhaskar R. Venepalli、Carl W. Griffin、Robert P. Gomez、Jay R. Wiggins、William R. Ingebretsen

  DOI：10.1021/jm00126a005

  日期：1989.6

  To examine the role of each component in the heterocycle-phenyl-imidazole inotropic pharmacophore, several imidazolone derivatives, an arylimidazole, a substituted 3,4-dihydro-4-oxopyrimidine, and a quinolin-2(1H)-one derivative were prepared as structural fragments or representatives from this relationship. Tests for cardiac inotropic activity in ferret papillary muscle strips (FPM) and for inhibition of crude cAMP phosphodiesterase obtained from canine cardiac tissue suggest that, while all three components contribute significantly toward potent activity (active at less than 1 microM concentrations in FPM), any combination of two components, in approximately a preferred geometry, represents the minimal requirements for weak activity (active at less than 25 microM concentrations). No single component appears to be requisite in an absolute sense.
• Chemistry and positive inotropic effect of pelrinone and related derivatives. A novel class of 2-methylpyrimidones as inotropic agents
  作者：Jehan Bagli、T. Bogri、B. Palameta、S. Rakhit、S. Peseckis、J. McQuillan、D. K. H. Lee

  DOI：10.1021/jm00399a023

  日期：1988.4

  A novel series of pyrimidine derivatives was synthesized and evaluated for positive inotropic activity. Inotropic and chronotropic effects were determined in vitro in cat papillary muscle and right atrium, respectively. Selected compounds were then evaluated in vivo in a dog heart failure model. Changes in ventricular dP/dt, heart rate, and blood pressure were monitored. Several of these agents produced relatively minor changes in heart rate. This class of agents demonstrated a varying degree of vasodilator effects concomitant with increases in ventricular contractility. The most potent analogues, 9, 48, and 49, were evaluated orally in conscious dogs with implanted Konisberg pressure transducers, and their effect on left ventricular dP/dt was compared with that of milrinone. Mechanistically, the agents of this novel class appear not to mediate their effect via beta-receptors or inhibition of Na+/K+-ATPase. A major component of their inotropic effect is mediated by the inhibition of cardiac phosphodiesterase (PDE)-Fr. III. This was clearly demonstrated by 9, 48, and 49. Compound 48 was found to be the most potent inhibitor of PDE-Fr. III from among the compounds tested in this assay.