4-氯-6-(甲基硫代)嘧啶-5-甲腈 | 150807-96-8

• 物质功能分类: 有机原料 - 杂环化合物
• 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-氯-6-(甲基硫代)嘧啶-5-甲腈
• 英文名称: 4-chloro-6-methylmercaptopyrimidine-5-carbonitrile
• 英文别名: 4-chloro-6-(methylthio)pyrimidine-5-carbonitrile；4-chloro-6-methylsulfanylpyrimidine-5-carbonitrile
• CAS: 150807-96-8
• 化学式: C₆H₄ClN₃S
• mdl: MFCD07761810
• 分子量: 185.637
• InChiKey: MTONZJLJGIIQRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 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：
  74.9
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-氯-6-(甲基硫代)嘧啶-5-甲腈 在 Oxone 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.08h， 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：

  4-甲基硫代-6-氧代-1,6-二氢嘧啶-5-甲腈 在 三氯氧磷 作用下， 反应 7.0h， 生成 4-氯-6-(甲基硫代)嘧啶-5-甲腈
  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

文献信息

• 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：——
• Suitably functionalised pyrimidines as potential antimycotic agents
  作者：Nidhi Agarwal、Sandeep K. Raghuwanshi、D.N. Upadhyay、P.K. Shukla、Vishnu J. Ram

  DOI：10.1016/s0960-894x(00)00091-3

  日期：2000.4

  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.
• Ram Vishnu J., Haque Navedul, Nath Mahendra, Indian J. Chem. B, 32 (1993) N 7, S 754-759
  作者：Ram Vishnu J., Haque Navedul, Nath Mahendra

  DOI：——

  日期：——
• 5-Cyanopyrimidine Derivatives as a Novel Class of Potent, Selective, and Orally Active Inhibitors of p38α MAP Kinase
  作者：Chunjian Liu、Stephen T. Wrobleski、James Lin、Gulzar Ahmed、Axel Metzger、John Wityak、Kathleen M. Gillooly、David J. Shuster、Kim W. McIntyre、Sidney Pitt、Ding Ren Shen、Rosemary F. Zhang、Hongjian Zhang、Arthur M. Doweyko、David Diller、Ian Henderson、Joel C. Barrish、John H. Dodd、Gary L. Schieven、Katerina Leftheris

  DOI：10.1021/jm0503594

  日期：2005.10.1

  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.