N-(2-bromo-4-isopropylphenyl)-4-carbomethoxy-6-methyl-pyrimidin-2-amine | 257615-17-1

• 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: N-(2-bromo-4-isopropylphenyl)-4-carbomethoxy-6-methyl-pyrimidin-2-amine
• 英文别名: 2-(N-(2-bromo-4-(2-propyl)phenyl)amino)-4-carbomethoxy-6-methylpyrimidinamine；2-(N-{2-bromo-4-(2-propyl)phenyl}amino)-4-carbomethoxy-6-methylpyrimidine；2-(N-(2-bromo-4-(2-propyl)phenyl)amino)-4-carbomethoxy-6-methylpyrimidine；methyl 2-(2-bromo-4-propan-2-ylanilino)-6-methylpyrimidine-4-carboxylate
• CAS: 257615-17-1
• 化学式: C₁₆H₁₈BrN₃O₂
• 分子量: 364.242
• InChiKey: RVADGLMNXSPVRI-UHFFFAOYSA-N

物化性质

• 沸点：
  476.8±55.0 °C(predicted)
• 密度：
  1.388±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  64.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-bromo-4-isopropylphenyl)-4-carbomethoxy-6-methyl-pyrimidin-2-amine 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Structure–activity studies on 4-substituted-2-anilinopyrimidine corticotropin releasing factor (CRF) antagonists

  摘要：

  Structure-activity studies around the 4-position of 2-anilinopyrimidine corticotropin releasing factor (CRF) antagonists suggest that there is a large lipophilic cavity in the rat CRF receptor, which can accommodate a wide variety of substituents at this position in contrast to the steric constraints observed for other positions on the 2-anilinopyrimidine core. The chemical syntheses and biological activities of 2-anilinopyrimidine CRF antagonists with carbon-linked substituents at the 4-position are reported. Significant improvements in rat pharmacokinetic parameters were achieved relative to those for the lead structure. While the lead compound 1 (rCRF K-i = 44 nM) afforded no detectable rat plasma levels after intraperitoneal tip) or oral (po) dosing, compounds 3-3 (rCRF K-i = 16 nM) and 3-3 (rCRF K-i = 59 nM) gave high rat plasma levels at 30 mg/kg (ip po) (C-max = 1389 nM and 8581 nM tip) respectively; C-max = 113 nM and 988 nM (po), respectively). Furthermore 3-3 and 3-4 had superior bioavailabilities at these doses (59 and 46% (ip), respectively: 2 and 10% (po), respectively). (C) 1999 DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00182-0
• 作为产物：
  描述：

  2-溴-4-异丙基苯胺 、 2-氯-6-甲基嘧啶-4-羧酸甲酯 在 碳酸氢钠 作用下， 以 1,4-二氧六环 为溶剂， 以47%的产率得到N-(2-bromo-4-isopropylphenyl)-4-carbomethoxy-6-methyl-pyrimidin-2-amine
  参考文献：
  名称：

  1N-alkyl-N-arylpyrimidinamines and derivatives thereof

  摘要：

  本发明提供了新颖的化合物、该化合物及其药物组合物，以及在治疗情感障碍、焦虑、抑郁症、创伤后应激障碍、进食障碍、上核性麻痹、肠易激综合征、免疫抑制、阿尔茨海默病、胃肠道疾病、厌食症、药物和酒精戒断症状、药物成瘾、炎症性疾病或生育问题中使用这些方法。本发明提供的新型化合物为以下式的化合物：##STR1## 其中R.sup.1、R.sup.3、R.sup.4、R.sup.5、Z、Y、V、X、X'、J、K、L和M如本文所定义。

  公开号：

  US06107301A1

文献信息

• 1N-alkyl-N-arylpyrimidinamines and derivatives thereof
  申请人：Dupont Pharmaceuticals Company

  公开号：US06107301A1

  公开（公告）日：2000-08-22

  The present invention provides novel compounds, compounds and pharmaceutical compositions thereof, and methods of using same in the treatment of affective disorders, anxiety, depression, post-traumatic stress disorders, eating disorders, supranuclear palsy, irritable bowel syndrome, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa, drug and alcohol withdrawal symptoms, drug addiction, inflammatory disorders, or fertility problems. The novel compounds provided by this invention are those of formula: ##STR1## wherein R.sup.1, R.sup.3, R.sup.4, R.sup.5, Z, Y, V, X, X', J, K, L, and M are as defined herein.

  本发明提供了新颖的化合物、该化合物及其药物组合物，以及在治疗情感障碍、焦虑、抑郁症、创伤后应激障碍、进食障碍、上核性麻痹、肠易激综合征、免疫抑制、阿尔茨海默病、胃肠道疾病、厌食症、药物和酒精戒断症状、药物成瘾、炎症性疾病或生育问题中使用这些方法。本发明提供的新型化合物为以下式的化合物：##STR1## 其中R.sup.1、R.sup.3、R.sup.4、R.sup.5、Z、Y、V、X、X'、J、K、L和M如本文所定义。
• 1N-alkyl-n-arylpyrimidinamines and derivatives thereof
  申请人：DuPont Pharmaceuticals Company

  公开号：US06342503B1

  公开（公告）日：2002-01-29

  The present invention provides novel compounds, compounds and pharmaceutical compositions thereof, and methods of using same in the treatment of affective disorders, anxiety, depression, post-traumatic stress disorders, eating disorders, supranuclear palsy, irritable bowel syndrome, immune suppression, Alzheimer'disease, gastrointestinal diseases, anorexia nervosa, drug and alcohol withdrawal symptoms, drug addiction, inflammatory disorders, or fertility problems. The novel compounds provided by this invention are those of formula: wherein R1, R3, R4, R5, Z, Y, V, X, X′, J, K, L, and M are as defined herein.

  本发明提供了新颖的化合物、该化合物及其药物组合物，以及在治疗情感障碍、焦虑、抑郁、创伤后应激障碍、进食障碍、上核性麻痹、肠易激综合征、免疫抑制、阿尔茨海默病、胃肠疾病、厌食症、药物和酒精戒断症状、药物成瘾、炎症性疾病或生育问题中使用这些方法。本发明提供的新型化合物为以下公式的化合物： 其中R1、R3、R4、R5、Z、Y、V、X、X'、J、K、L和M如本文所定义。
• 1N-ALKYL-N-ARYLPYRIMIDINAMINES AND DERIVATIVES THEREOF
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：EP0723533A1

  公开（公告）日：1996-07-31
• US6107301A
  申请人：——

  公开号：US6107301A

  公开（公告）日：2000-08-22
• US6342503B1
  申请人：——

  公开号：US6342503B1

  公开（公告）日：2002-01-29