1-(2,6-difluoro-benzyl)-3-{2-[methyl-(2-pyridin-2-yl-ethyl)-amino]-ethyl}-5,6,7,8-tetrahydro-1H-pyrido[4,3-d]pyrimidine-2,4-dione | 947403-80-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 1-(2,6-difluoro-benzyl)-3-{2-[methyl-(2-pyridin-2-yl-ethyl)-amino]-ethyl}-5,6,7,8-tetrahydro-1H-pyrido[4,3-d]pyrimidine-2,4-dione
• 英文别名: 1-[(2,6-difluorophenyl)methyl]-3-[2-[methyl(2-pyridin-2-ylethyl)amino]ethyl]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-2,4-dione
• CAS: 947403-80-7
• 化学式: C₂₄H₂₇F₂N₅O₂
• 分子量: 455.507
• InChiKey: DEJXGNZNGZIZTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2,6-difluoro-benzyl)-3-{2-[methyl-(2-pyridin-2-yl-ethyl)-amino]-ethyl}-5,6,7,8-tetrahydro-1H-pyrido[4,3-d]pyrimidine-2,4-dione 、 1-(4-甲醛基苯基)咪唑 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 1-(2,6-difluorobenzyl)-6-(4-(1H-imidazol-1-yl)benzyl)-3-(2-(methyl(2-(pyridin-2-yl)ethyl)amino)ethyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Selection, synthesis, and structure–activity relationship of tetrahydropyrido[4,3-d]pyrimidine-2,4-diones as human GnRH receptor antagonists

  摘要：

  The present article describes a selection of a new class of small molecule antagonists for the h-GnRH receptor, their preparation, and evaluation in vitro. Three computational methods were combined into a consensus score, to rank order virtual templates. The top 5% of templates were further evaluated in silico and assessed for novelty and synthetic accessibility. The tetrahydropyrido[4,3-d]pyrimidine-2,4-dione core was selected for synthesis and evaluated in vitro. Using an array approach for analog design and synthesis, we were able to drive the binding below 10 nM for the h-GnRH receptor after two rounds of optimization. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.029
• 作为产物：
  描述：

  1-(2,6-difluorobenzyl)-3-{2-[methyl(2-pyridin-2-ylethyl)amino]ethyl}-2,4-dioxo-1,3,4,5,7,8-hexahydro-2H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 1-(2,6-difluoro-benzyl)-3-{2-[methyl-(2-pyridin-2-yl-ethyl)-amino]-ethyl}-5,6,7,8-tetrahydro-1H-pyrido[4,3-d]pyrimidine-2,4-dione
  参考文献：
  名称：

  Selection, synthesis, and structure–activity relationship of tetrahydropyrido[4,3-d]pyrimidine-2,4-diones as human GnRH receptor antagonists

  摘要：

  The present article describes a selection of a new class of small molecule antagonists for the h-GnRH receptor, their preparation, and evaluation in vitro. Three computational methods were combined into a consensus score, to rank order virtual templates. The top 5% of templates were further evaluated in silico and assessed for novelty and synthetic accessibility. The tetrahydropyrido[4,3-d]pyrimidine-2,4-dione core was selected for synthesis and evaluated in vitro. Using an array approach for analog design and synthesis, we were able to drive the binding below 10 nM for the h-GnRH receptor after two rounds of optimization. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.029

文献信息

• Selection, synthesis, and structure–activity relationship of tetrahydropyrido[4,3-d]pyrimidine-2,4-diones as human GnRH receptor antagonists
  作者：Marion C. Lanier、Miklos Feher、Neil J. Ashweek、Colin J. Loweth、Jaimie K. Rueter、Deborah H. Slee、John P. Williams、Yun-Fei Zhu、Susan K. Sullivan、Michael S. Brown

  DOI：10.1016/j.bmc.2007.05.029

  日期：2007.8

  The present article describes a selection of a new class of small molecule antagonists for the h-GnRH receptor, their preparation, and evaluation in vitro. Three computational methods were combined into a consensus score, to rank order virtual templates. The top 5% of templates were further evaluated in silico and assessed for novelty and synthetic accessibility. The tetrahydropyrido[4,3-d]pyrimidine-2,4-dione core was selected for synthesis and evaluated in vitro. Using an array approach for analog design and synthesis, we were able to drive the binding below 10 nM for the h-GnRH receptor after two rounds of optimization. (c) 2007 Elsevier Ltd. All rights reserved.