5,6-diamino-1-(2,4-dichlorophenyl)-3-methyl-2,4(1H,3H)-pyrimidinedione | 488705-85-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5,6-diamino-1-(2,4-dichlorophenyl)-3-methyl-2,4(1H,3H)-pyrimidinedione
• 英文别名: 5,6-Diamino-1-(2,4-dichlorophenyl)-3-methylpyrimidine-2,4-dione
• CAS: 488705-85-7
• 化学式: C₁₁H₁₀Cl₂N₄O₂
• 分子量: 301.132
• InChiKey: URBFTSODWUUKLN-UHFFFAOYSA-N

物化性质

• 熔点：
  170-172.5 °C
• 沸点：
  413.4±55.0 °C(Predicted)
• 密度：
  1.551±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6-diamino-1-(2,4-dichlorophenyl)-3-methyl-2,4(1H,3H)-pyrimidinedione 在 sodium hydroxide 、 四丁基碘化铵 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.83h， 生成 1-(benzyloxymethyl)-4-[(2,4-dichlorophenyl)amino]-2-ethyl-N-methyl-1H-imidazole-5-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 1,2,3,7-Tetrahydro-6H-purin-6-one and 3,7-Dihydro-1H-purine-2,6-dione Derivatives as Corticotropin-Releasing Factor₁ Receptor Antagonists

  摘要：

  A growing body of evidence suggests that CRF1, receptor antagonism offers considerable therapeutic potential in the treatment of diseases resulting from elevated levels of CRF, such as anxiety and depression. A series of novel 1,2,3,7-tetrahydro-6H-purin-6-one and 3,7-dihydro-1H-purine-2,6-dione derivatives was synthesized and evaluated as corticotropin releasing factor-1 (CRF1) receptor antagonists. Compounds within this series, represented by compound 12d (IC50 = 5.4 nM), were found to be highly potent CRF, receptor antagonists. In addition, compounds 12d and 12j were determined to be selective CRF, antagonists. The synthesis, structure-activity relationships and pharmacokinetic properties of compounds within this series is presented.

  DOI：

  10.1021/jm049787k
• 作为产物：
  描述：

  2,4-二氯苯基异氰酸酯 在 ammonium hydroxide 、 sodium dithionite 、 乙酸酐 、 溶剂黄146 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 12.58h， 生成 5,6-diamino-1-(2,4-dichlorophenyl)-3-methyl-2,4(1H,3H)-pyrimidinedione
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 1,2,3,7-Tetrahydro-6H-purin-6-one and 3,7-Dihydro-1H-purine-2,6-dione Derivatives as Corticotropin-Releasing Factor₁ Receptor Antagonists

  摘要：

  A growing body of evidence suggests that CRF1, receptor antagonism offers considerable therapeutic potential in the treatment of diseases resulting from elevated levels of CRF, such as anxiety and depression. A series of novel 1,2,3,7-tetrahydro-6H-purin-6-one and 3,7-dihydro-1H-purine-2,6-dione derivatives was synthesized and evaluated as corticotropin releasing factor-1 (CRF1) receptor antagonists. Compounds within this series, represented by compound 12d (IC50 = 5.4 nM), were found to be highly potent CRF, receptor antagonists. In addition, compounds 12d and 12j were determined to be selective CRF, antagonists. The synthesis, structure-activity relationships and pharmacokinetic properties of compounds within this series is presented.

  DOI：

  10.1021/jm049787k

文献信息

• 3,7-dihydro-purine-2,6-dione derivatives as CRF receptor ligands
  申请人：——

  公开号：US20030119831A1

  公开（公告）日：2003-06-26

  Compounds provided herein are 3,7-dihydro-purine-2,6-dione derivatives of Formula (I): 1 Such compounds are particularly useful as CRF receptor ligands, and hence, in the treatment of various neurologically-related disorders such as affective disorder, anxiety and depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis or hypoglycemia.

  本文提供的化合物是Formula (I)的3,7-二氢嘌呤-2,6-二酮衍生物。这些化合物特别适用作为CRF受体配体，因此在治疗各种神经相关疾病方面特别有用，如情感障碍、焦虑和抑郁症、头痛、肠易激综合征、创伤后应激障碍、上核性麻痹、免疫抑制、阿尔茨海默病、胃肠疾病、厌食症或其他进食障碍、药物成瘾、药物或酒精戒断症状、炎症性疾病、心血管或心脏相关疾病、生育问题、人类免疫缺陷病毒感染、出血性应激、肥胖、不孕症、头部和脊髓创伤、癫痫、中风、溃疡、肌萎缩性侧索硬化或低血糖症。
• Tetrahydropurinones and derivatives thereof as corticotropin releasing factor receptor ligands
  申请人：——

  公开号：US20030149059A1

  公开（公告）日：2003-08-07

  Compounds provided herein are novel substituted tetrahydropurinones of Formula (I): 1 Such compounds are particularly useful as CRF receptor ligands, and hence, in the treatment of various neurologically-related disorders such as affective disorder, anxiety and depression.

  本文提供的化合物是具有式(I)的新型取代四氢嘌呤酮。这些化合物特别适用作为CRF受体配体，因此在治疗各种神经相关疾病，如情感障碍、焦虑和抑郁症方面具有重要作用。
• US6894045B2
  申请人：——

  公开号：US6894045B2

  公开（公告）日：2005-05-17
• US7098217B2
  申请人：——

  公开号：US7098217B2

  公开（公告）日：2006-08-29
• Design, Synthesis, and Biological Evaluation of 1,2,3,7-Tetrahydro-6<i>H</i>-purin-6-one and 3,7-Dihydro-1<i>H</i>-purine-2,6-dione Derivatives as Corticotropin-Releasing Factor₁ Receptor Antagonists
  作者：Richard A. Hartz、Kausik K. Nanda、Charles L. Ingalls、Vijay T. Ahuja、Thaddeus F. Molski、Ge Zhang、Harvey Wong、Yong Peng、Michelle Kelley、Nicholas J. Lodge、Robert Zaczek、Paul J. Gilligan、George L. Trainor

  DOI：10.1021/jm049787k

  日期：2004.9.1

  A growing body of evidence suggests that CRF1, receptor antagonism offers considerable therapeutic potential in the treatment of diseases resulting from elevated levels of CRF, such as anxiety and depression. A series of novel 1,2,3,7-tetrahydro-6H-purin-6-one and 3,7-dihydro-1H-purine-2,6-dione derivatives was synthesized and evaluated as corticotropin releasing factor-1 (CRF1) receptor antagonists. Compounds within this series, represented by compound 12d (IC50 = 5.4 nM), were found to be highly potent CRF, receptor antagonists. In addition, compounds 12d and 12j were determined to be selective CRF, antagonists. The synthesis, structure-activity relationships and pharmacokinetic properties of compounds within this series is presented.