4-chloro-2-(ethylthio)-4-(methylthio)pyrimidine-5-carbonitrile | 868272-42-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-chloro-2-(ethylthio)-4-(methylthio)pyrimidine-5-carbonitrile
• 英文别名: 4-chloro-2-(ethylthio)-6-(methylthio)pyrimidine-5-carbonitrile；4-Chloro-2-ethylsulfanyl-6-methylsulfanyl-pyrimidine-5-carbonitrile；4-chloro-2-ethylsulfanyl-6-methylsulfanylpyrimidine-5-carbonitrile
• CAS: 868272-42-8
• 化学式: C₈H₈ClN₃S₂
• 分子量: 245.757
• InChiKey: JNDUCEXISBYVPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  100
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-chloro-2-(ethylthio)-4-(methylthio)pyrimidine-5-carbonitrile 在 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.5h， 生成 tert-butyl (1S,2R)-2-(4-(3-(2H-1,2,3-triazol-2-yl)phenylamino)-5 cyano-6-(methylthio)pyrimidin-2-ylamino)cyclohexylcarbamate
  参考文献：
  名称：

  [EN] OXYPYRIMIDINES AS SYK MODULATORS
  [FR] OXYPYRIMIDINES EN TANT QUE MODULATEURS DE SYK

  摘要：

  本发明涉及式(I)的化合物及其互变异构体或药用可接受的盐、酯和前药，其为Syk激酶的抑制剂。本发明还涉及用于制备这种化合物的中间体，该化合物的制备，含有该化合物的药物组合物，抑制Syk激酶活性的方法，抑制血小板聚集的方法，以及预防或治疗至少部分由Syk激酶活性介导的多种疾病的方法，如不良血栓形成和非霍奇金淋巴瘤。

  公开号：

  WO2012061415A1
• 作为产物：
  描述：

  2-(ethylthio)-4-(methylthio)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 在 三氯氧磷 作用下， 反应 1.5h， 以1.72 g的产率得到4-chloro-2-(ethylthio)-4-(methylthio)pyrimidine-5-carbonitrile
  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

• OXYPYRIMIDINES AS SYK MODULATORS
  申请人：Pandey Anjali

  公开号：US20130317029A1

  公开（公告）日：2013-11-28

  The present invention is directed to compounds of formula (I) and tautomers thereof or pharmaceutically acceptable salts, esters, and prodrugs thereof which arc inhibitor of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as undesired thrombosis and Non Hodgkin's Lymphoma.

  本发明涉及以下式（I）的化合物及其互变异构体或药学上可接受的盐、酯和前药，其为Syk激酶的抑制剂。本发明还涉及制备这种化合物所使用的中间体，制备这种化合物的方法，含有这种化合物的药物组合物，抑制Syk激酶活性的方法，抑制血小板聚集的方法，以及预防或治疗至少部分由Syk激酶活性介导的多种疾病，例如不良血栓形成和非何杰金淋巴瘤的方法。
• 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.
• [EN] OXYPYRIMIDINES AS SYK MODULATORS<br/>[FR] OXYPYRIMIDINES EN TANT QUE MODULATEURS DE SYK
  申请人：PORTOLA PHARM INC

  公开号：WO2012061415A1

  公开（公告）日：2012-05-10

  The present invention is directed to compounds of formula (I) and tautomers thereof or pharmaceutically acceptable salts, esters, and prodrugs thereof which arc inhibitor of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as undesired thrombosis and Non Hodgkin's Lymphoma.

  本发明涉及式(I)的化合物及其互变异构体或药用可接受的盐、酯和前药，其为Syk激酶的抑制剂。本发明还涉及用于制备这种化合物的中间体，该化合物的制备，含有该化合物的药物组合物，抑制Syk激酶活性的方法，抑制血小板聚集的方法，以及预防或治疗至少部分由Syk激酶活性介导的多种疾病的方法，如不良血栓形成和非霍奇金淋巴瘤。