2,5-diamino-6-chloro-4-(isopropylamino)pyrimidine | 343327-12-8

• 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: 2,5-diamino-6-chloro-4-(isopropylamino)pyrimidine
• 英文别名: 6-Chloro-4-N-(propan-2-YL)pyrimidine-2,4,5-triamine；6-chloro-4-N-propan-2-ylpyrimidine-2,4,5-triamine
• CAS: 343327-12-8
• 化学式: C₇H₁₂ClN₅
• 分子量: 201.659
• InChiKey: CNYHXCROGLKAFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  89.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,5-diamino-6-chloro-4-(isopropylamino)pyrimidine 在 盐酸 、 copper(l) iodide 、 二碘甲烷 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 为溶剂， 生成 6-chloro-2-iodo-9-isopropylpurine
  参考文献：
  名称：

  Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines acting as cyclin-dependent kinase inhibitors

  摘要：

  Novel C-2, C-6, N-9 trisubstituted purines derived from the olomoucine/roscovitine lead structure were synthesized and evaluated for their ability to inhibit starfish oocyte CDK1/cyclin B, neuronal CDK5/p35 and erk1 kinases in purified extracts. Structure-activity relationship studies showed that increased steric bulk at N-9 reduces the inhibitory potential whereas substitution of the aminoethanol C-2 side chain by various groups of different size (methyl, propyl, butyl, phenyl, benzyl) only slightly decreases the activity when compared to (R)-roscovitine. Optimal inhibitory activity against CDK5, CDK1 and CDK2, with IC50 values of 0.16, 0.45 and 0.65 mu M, respectively, was obtained with compound 21 containing a (2R)-pyrrolidin-2-yl-methanol substituent at the C-2 and a 3-iodobenzylamino group at the C-6 of the purine. Compound 21 proved cytotoxic against human tumor HeLa cells (LD50 = 6.7 mu M versus 42.7 mu M for olomoucine, 24-h contact). Furthermore, unlike olomoucine, compound 21 was effective upon short exposure (LD50 = 25.3 mu M, 2-h contact). The available data suggest that the affinity for CDKs and the cytotoxic potential of the drugs are inter-related. However, no straightforward cell cycle phase specificity of the cytotoxic response to 21 was observed in synchronized HeLa cells. With the noticeable exception of pronounced lengthening of the S-phase transit by 21 applied during early-S in synchronized HeLa cells, and in striking contrast with earlier reports on studies using plant or echinoderm cells, olomoucine and compound 21 were unable to reversibly arrest cell cycle progression in asynchronous growing HeLa cells. Some irreversible block in G1 and G2 phase occurred at high olomoucine concentration, correlated with induced cell death. Moreover, chronic exposure to lethal doses of compound 21 resulted in massive nuclear fragmentation, evocative of mitotic catastrophe with minor amounts of apoptosis only. It was also found that olomoucine and compound 21 reversibly block the intracellular uptake of nucleosides with high efficiency. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00064-4
• 作为产物：
  描述：

  2,5-二氨基-4,6-二氯嘧啶 、 异丙胺 在 碳酸氢钠 作用下， 以 正丁醇 为溶剂， 反应 2.0h， 以58%的产率得到2,5-diamino-6-chloro-4-(isopropylamino)pyrimidine
  参考文献：
  名称：

  6-烷氧基嘌呤类似物作为 Jurkat 细胞细胞类型选择性凋亡诱导剂的合成与筛选

  摘要：

  嘌呤是细胞生物学中普遍存在的结构，涉及多种细胞过程，因此取代的嘌呤和类似物被认为是药物设计中的优秀支架。在这项研究中，我们通过建立 6-烷氧基嘌呤文库，探索了基于嘌呤的促凋亡基因 8- tert -butyl-9-phenyl-6-benzyloxy-9 H -purine ( 1 ) 的关键结构特征目的是阐明控制其生物活性的结构要求并研究这种化学型的细胞选择性。这是通过基于六种人类癌细胞系（包括 T 细胞白血病 Jurkat 细胞）的细胞周期分析的表型筛选方法完成的。从这项研究中，两个衍生品（12和13) 被鉴定为 Jurkat 选择性促凋亡化合物，显示出比 hit 1更好的效力和细胞选择性。

  DOI：

  10.1002/ardp.202100095

文献信息

• Dipeptidyl peptidase inhibitors
  申请人：Syrrx, Inc.

  公开号：US20040259870A1

  公开（公告）日：2004-12-23

  Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 protease that comprise a compound comprising the formula: 1 wherein Q is selected from the group of CO, SO, SO 2 , or C═NR 9 ; and R 1 , R 2 , R 3 and R 4 are as defined herein.

  提供了与DPP-IV和其他S9蛋白酶一起使用的化合物、药物、试剂盒和方法，其中包括具有以下式子的化合物：1，其中Q是从CO、SO、SO2或C═NR9;组中选择的，而R1、R2、R3和R4如在此定义。
• DIPEPTIDYL PEPTIDASE INHIBITORS
  申请人：Takeda San Diego, Inc.

  公开号：EP1608317A2

  公开（公告）日：2005-12-28
• EP1608317A4
  申请人：——

  公开号：EP1608317A4

  公开（公告）日：2006-12-27
• US7550590B2
  申请人：——

  公开号：US7550590B2

  公开（公告）日：2009-06-23
• US7687625B2
  申请人：——

  公开号：US7687625B2

  公开（公告）日：2010-03-30