{2-[(2-Bromo-4-isopropyl-phenyl)-ethyl-amino]-6-methyl-pyrimidin-4-yl}-(2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-methanone | 169881-55-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: {2-[(2-Bromo-4-isopropyl-phenyl)-ethyl-amino]-6-methyl-pyrimidin-4-yl}-(2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-methanone
• CAS: 169881-55-4
• 化学式: C₂₅H₃₀BrN₇O
• 分子量: 524.463
• InChiKey: GKGXYCGKSJBCJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.58
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  78.35
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  {2-[(2-Bromo-4-isopropyl-phenyl)-ethyl-amino]-6-methyl-pyrimidin-4-yl}-(2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-methanone 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 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-氯-6-甲基嘧啶-4-羧酸甲酯 在 sodium hydride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 {2-[(2-Bromo-4-isopropyl-phenyl)-ethyl-amino]-6-methyl-pyrimidin-4-yl}-(2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-methanone
  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