2-methyl-5-nitro-4-(2,4,6-trimethylanilino)-1H-pyrimidin-6-one | 197802-86-1

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-methyl-5-nitro-4-(2,4,6-trimethylanilino)-1H-pyrimidin-6-one
• CAS: 197802-86-1
• 化学式: C₁₄H₁₆N₄O₃
• 分子量: 288.306
• InChiKey: SDRCWBFJKHJCEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  99.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methyl-5-nitro-4-(2,4,6-trimethylanilino)-1H-pyrimidin-6-one 在 铁粉 、 溶剂黄146 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 4.5h， 生成 6-chloro-2-methyl-4-N-(2,4,6-trimethylphenyl)pyrimidine-4,5-diamine
  参考文献：
  名称：

  Purin-8-ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists

  摘要：

  A series of purin-8-ones was prepared and discovered to have excellent binding affintity to the CRH-R1 receptor. Structure-activity studies focused on amine side-chain optimization, urea substitution and pyridyl isostere incorporation. Thus, the highly potent purin-8-ones show promise as a new class of potential anxiolytics and/or antidepressants. (C) 1999 DuPont Pharmaceuticals. Published by Elsevier Science I,td. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00108-0
• 作为产物：
  描述：

  2-甲基-4,6-二羟基嘧啶 在 硝酸 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 二甲基亚砜 为溶剂， 反应 21.5h， 生成 2-methyl-5-nitro-4-(2,4,6-trimethylanilino)-1H-pyrimidin-6-one
  参考文献：
  名称：

  Purin-8-ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists

  摘要：

  A series of purin-8-ones was prepared and discovered to have excellent binding affintity to the CRH-R1 receptor. Structure-activity studies focused on amine side-chain optimization, urea substitution and pyridyl isostere incorporation. Thus, the highly potent purin-8-ones show promise as a new class of potential anxiolytics and/or antidepressants. (C) 1999 DuPont Pharmaceuticals. Published by Elsevier Science I,td. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00108-0

文献信息

• Synthesis, Corticotropin-Releasing Factor Receptor Binding Affinity, and Pharmacokinetic Properties of Triazolo-, Imidazo-, and Pyrrolopyrimidines and -pyridines
  作者：Robert J. Chorvat、Rajagopal Bakthavatchalam、James P. Beck、Paul J. Gilligan、Richard G. Wilde、Anthony J. Cocuzza、Frank W. Hobbs、Robert S. Cheeseman、Matthew Curry、Joseph P. Rescinito、Paul Krenitsky、Dennis Chidester、Jerry A. Yarem、John D. Klaczkiewicz、C. Nicholas Hodge、Paul E. Aldrich、Zelda R. Wasserman、Christine H. Fernandez、Robert Zaczek、Lawrence W. Fitzgerald、Shiew-Mei Huang、Helen L. Shen、Y. Nancy Wong、Ben M. Chien、Check Y. Quon、Argyrios Arvanitis

  DOI：10.1021/jm980224g

  日期：1999.3.1

  The synthesis and CRF receptor binding affinities of several new series of N-aryltriazolo- and -imidazopyrimidines and -pyridines are described. These cyclized systems were prepared from appropriately substituted diaminopyrimidines or -pyridines by nitrous acid, orthoester, or acyl halide treatment. Variations of amino (ether) pendants and aromatic substituents have defined the structure-activity relationships

  描述了几种新系列的N-芳基三唑-和-咪唑并嘧啶和-吡啶的合成和CRF受体结合亲和力。这些环化体系是由适当取代的二氨基嘧啶或-吡啶通过亚硝酸，原酸酯或酰卤处理制得的。氨基（醚）侧基和芳族取代基的变化定义了这些系列的结构-活性关系，并导致鉴定出多种高亲和力试剂（Ki's <10 nM）。基于该性质和亲脂性差异，最初选择了其中的六个化合物（4d，i，n，x，8k，9a）用于大鼠药代动力学（PK）研究。良好的口服生物利用度，高血浆水平以及四种化合物的持续时间（4d，i，n，x）提示在静脉内和口服给药后都对狗进行了进一步的PK研究。这项工作的结果表明4i，x具有我们认为是潜在治疗剂所必需的特性，并且已选择4i1进行进一步的药理研究，并将在适当时候进行报道。
• Purin-8-ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists
  作者：James P. Beck、Argyrios G. Arvanitis、Matt A. Curry、Joseph T. Rescinito、Larry W. Fitzgerald、Paul J. Gilligan、Robert Zaczek、George L. Trainor

  DOI：10.1016/s0960-894x(99)00108-0

  日期：1999.4

  A series of purin-8-ones was prepared and discovered to have excellent binding affintity to the CRH-R1 receptor. Structure-activity studies focused on amine side-chain optimization, urea substitution and pyridyl isostere incorporation. Thus, the highly potent purin-8-ones show promise as a new class of potential anxiolytics and/or antidepressants. (C) 1999 DuPont Pharmaceuticals. Published by Elsevier Science I,td. All rights reserved.