2-chloro-4-phenylamino-6-propylamino-1,3,5-triazine | 185680-82-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 2-chloro-4-phenylamino-6-propylamino-1,3,5-triazine
• 英文别名: 6-Chloro-N~2~-phenyl-N~4~-propyl-1,3,5-triazine-2,4-diamine；6-chloro-2-N-phenyl-4-N-propyl-1,3,5-triazine-2,4-diamine
• CAS: 185680-82-4
• 化学式: C₁₂H₁₄ClN₅
• 分子量: 263.73
• InChiKey: XFDYUYFSGZGZID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  62.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  potassium cyanide 、 2-chloro-4-phenylamino-6-propylamino-1,3,5-triazine 以 二甲基亚砜 为溶剂， 反应 0.17h， 以220 mg的产率得到4-(phenylamino)-6-(propylamino)-1,3,5-triazine-2-carbonitrile
  参考文献：
  名称：

  Identification and Optimization of Inhibitors of Trypanosomal Cysteine Proteases: Cruzain, Rhodesain, and TbCatB

  摘要：

  Trypanosoma cruzi and Trypanosoma brucei are parasites that cause Chagas' disease and African sleeping sickness, respectively. Both parasites rely oil essential cysteine proteases for survival: cruzain for T. cruzi and TbCatB/rhodesain for T. brucei. A recent quantitative high-throughput screen of cruzain identified triazine nitriles. which are known inhibitors of other cysteine proteases, its reversible inhibitors of the enzyme. Structural modifications detailed herein, including core scaffold modification from triazine to purine, improved the in vitro potency against both cruzain and rhodesain by 350-fold, while also gaining activity against T. brucei parasites. Selected compounds were screened against it panel of human cysteine and serine proteases to determine selectivity, and it cocrystal was obtained of our most potent analogue bound to cruzain.

  DOI：

  10.1021/jm901069a
• 作为产物：
  描述：

  2,4-Dichlor-6-propylamino-s-triazin 、 苯胺 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.08h， 生成 2-chloro-4-phenylamino-6-propylamino-1,3,5-triazine
  参考文献：
  名称：

  Identification and Optimization of Inhibitors of Trypanosomal Cysteine Proteases: Cruzain, Rhodesain, and TbCatB

  摘要：

  Trypanosoma cruzi and Trypanosoma brucei are parasites that cause Chagas' disease and African sleeping sickness, respectively. Both parasites rely oil essential cysteine proteases for survival: cruzain for T. cruzi and TbCatB/rhodesain for T. brucei. A recent quantitative high-throughput screen of cruzain identified triazine nitriles. which are known inhibitors of other cysteine proteases, its reversible inhibitors of the enzyme. Structural modifications detailed herein, including core scaffold modification from triazine to purine, improved the in vitro potency against both cruzain and rhodesain by 350-fold, while also gaining activity against T. brucei parasites. Selected compounds were screened against it panel of human cysteine and serine proteases to determine selectivity, and it cocrystal was obtained of our most potent analogue bound to cruzain.

  DOI：

  10.1021/jm901069a

文献信息

• [EN] 2-CYANO-1,3,5-TRIAZINE-4,6-DIAMINE DERIVATIVES<br/>[FR] DERIVES 2-CYANO-1,3,5-TRIAZINE-4,6-DIAMINES
  申请人：AKZO NOBEL NV

  公开号：WO2005011703A1

  公开（公告）日：2005-02-10

  The invention relates to the use of a 2-cyano-1,3,5-triazine -4,6-diamine derivative having general formula (I), wherein R1 is (C1-6)alkyl, (C3-8)cycloalkyl, aryl, aryl(C1-4)alkyl, aryloxy(C1-4)alkyl, heteroaryl or heteroaryloxy(C1-4)alkyl; R2 is H or (C1-4)alkyl; or R1 and R2 together with the nitrogen to which they are bound form a 4-8 membered heterocyclic ring, optionally further comprising 1 or more heteroatoms selected from O, S or NR5, which ring may be substituted with (C1-4)alkyl, (C3-8)cycloalkyl, aryl, aryl(C1-4)alkyl or NR6R7,and which ring may be fused to a benzene ring; R3 is (C1-6)alkyl, (C3-8) cycloalkyl (optionally comprising 1 or more heteroatoms selected from O, S or NR8), aryl, aryl(C1-4)alkyl or heteroaryl; R4 is H or (C1-4)alkyl; or R3 and R4 together with the nitrogen to which they are bound form a 4-8 membered heterocyclic ring, optionally further comprising 1 or more heteroatoms selected from O, S or NR9; R5, R8 and R9 are independently H, (C1-4)alkyl, (C3-8) cycloalkyl, aryl or aryl(C1-4)alkyl; R6 and R7 are independently H or (C1-4)alkyl; or R6 and R7 form together with the nitrogen to which they are bound a 4-8 membered heterocyclic ring; or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of osteoporosis and atherosclerosis.

  该发明涉及使用具有通式（I）的2-氰基-1,3,5-三嗪-4,6-二胺衍生物，其中R1为（C1-6）烷基，（C3-8）环烷基，芳基，芳基（C1-4）烷基，芳氧基（C1-4）烷基，杂芳基或杂芳氧基（C1-4）烷基；R2为H或（C1-4）烷基；或R1和R2与它们结合的氮一起形成一个4-8元杂环，可进一步包括1个或多个来自O、S或NR5的杂原子，该环可能被（C1-4）烷基，（C3-8）环烷基，芳基，芳基（C1-4）烷基或NR6R7取代，并且该环可能与苯环融合；R3为（C1-6）烷基，（C3-8）环烷基（可包括来自O、S或NR8的1个或多个杂原子），芳基，芳基（C1-4）烷基或杂芳基；R4为H或（C1-4）烷基；或R3和R4与它们结合的氮一起形成一个4-8元杂环，可进一步包括1个或多个来自O、S或NR9的杂原子；R5、R8和R9独立地为H，（C1-4）烷基，（C3-8）环烷基，芳基或芳基（C1-4）烷基；R6和R7独立地为H或（C1-4）烷基；或R6和R7与它们结合的氮一起形成一个4-8元杂环；或其药学上可接受的盐，用于制备治疗骨质疏松症和动脉粥样硬化的药物。
• Identification and Optimization of Inhibitors of Trypanosomal Cysteine Proteases: Cruzain, Rhodesain, and TbCatB
  作者：Bryan T. Mott、Rafaela S. Ferreira、Anton Simeonov、Ajit Jadhav、Kenny Kean-Hooi Ang、William Leister、Min Shen、Julia T. Silveira、Patricia S. Doyle、Michelle R. Arkin、James H. McKerrow、James Inglese、Christopher P. Austin、Craig J. Thomas、Brian K. Shoichet、David J. Maloney

  DOI：10.1021/jm901069a

  日期：2010.1.14

  Trypanosoma cruzi and Trypanosoma brucei are parasites that cause Chagas' disease and African sleeping sickness, respectively. Both parasites rely oil essential cysteine proteases for survival: cruzain for T. cruzi and TbCatB/rhodesain for T. brucei. A recent quantitative high-throughput screen of cruzain identified triazine nitriles. which are known inhibitors of other cysteine proteases, its reversible inhibitors of the enzyme. Structural modifications detailed herein, including core scaffold modification from triazine to purine, improved the in vitro potency against both cruzain and rhodesain by 350-fold, while also gaining activity against T. brucei parasites. Selected compounds were screened against it panel of human cysteine and serine proteases to determine selectivity, and it cocrystal was obtained of our most potent analogue bound to cruzain.