5-methoxy-2-(pyridin-2-yl)-N-[2-(trifluoromethyl)benzyl]pyrimidin-4-amine | 1393899-43-8

• 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: 5-methoxy-2-(pyridin-2-yl)-N-[2-(trifluoromethyl)benzyl]pyrimidin-4-amine
• 英文别名: 5-methoxy-2-pyridin-2-yl-N-[[2-(trifluoromethyl)phenyl]methyl]pyrimidin-4-amine
• CAS: 1393899-43-8
• 化学式: C₁₈H₁₅F₃N₄O
• 分子量: 360.339
• InChiKey: GZIPJTDUDKQMMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(三氟甲基)苄胺 、 4-氯-5-甲氧基-2-(2-吡啶)嘧啶 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 72.0h， 以55%的产率得到5-methoxy-2-(pyridin-2-yl)-N-[2-(trifluoromethyl)benzyl]pyrimidin-4-amine
  参考文献：
  名称：

  Orally available pyridinylpyrimidine derivatives as novel RANKL-induced osteoclastogenesis inhibitors

  摘要：

  An HTS campaign led to the identification of 4-pyrroldino-2-(pyridin-2-yl) pyrimidine compound 1 as an RANKL-induced osteoclastogenesis inhibitor. The compound 1 showed high clearance values in microsomes, however. Modification of the pyrrolidino group to a benzylamino group improved human microsomal stability with a slight loss of in vitro activity. Substitution at the ortho position of the benzyl group ameliorated in vitro activity, and further fluorination of the benzyl group improved microsomal stability in rodents. Representative members of this series, compounds 20 and 23, exhibited efficacy in RANKL-induced osteopenic mice when administered orally at 0.3 mg/kg. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.087

文献信息

• [EN] 2-(PYRIDINE-2-YL)PYRIMIDINE-4-AMINE COMPOUND AND SALT THEREOF<br/>[FR] COMPOSÉ 2-(PYRIDINE-2-YL)PYRIMIDINE-4-AMINE ET SEL DE CELUI-CI
  申请人：ASTELLAS PHARMA INC

  公开号：WO2013047719A1

  公开（公告）日：2013-04-04

  　骨粗鬆症、骨減少症、関節リウマチ等のRANKL/RANKシグナルが関与する疾患の治療用医薬組成物の有効成分として有用な化合物を提供する。　本発明者らは、RANKL/RANKシグナル阻害活性を有する化合物について検討し、2-(ピリジン-2-イル)ピリミジン-4-アミン化合物又はその塩がRANKL/RANKシグナル阻害活性を有すること、RANKL誘発骨塩量減少を改善すること、並びに、骨粗鬆症モデル及び関節炎モデルで有効であることを確認し、本発明を完成した。本発明の2-(ピリジン-2-イル)ピリミジン-4-アミン化合物又はその塩はRANKL/RANKシグナル阻害活性を有し、骨粗鬆症、骨減少症、関節リウマチ等のRANKL/RANKシグナルが関与する疾患の治療剤として使用しうる。
• Orally available pyridinylpyrimidine derivatives as novel RANKL-induced osteoclastogenesis inhibitors
  作者：Junji Miyata、Chiyoshi Kasahara、Toru Asano、Shinji Ito、Norio Seki、Yasuko Kato、Noriyuki Morikawa、Kazuyoshi Nozaki、Kouji Nishimura、Hisashi Akamatsu、Yusuke Taguchi、Tomonori Yamaguchi、Yoshito Abe、Mitsuru Ohkubo、Toshihiro Watanabe、Mitsuaki Ohta、Makoto Takeuchi

  DOI：10.1016/j.bmcl.2012.06.087

  日期：2012.9

  An HTS campaign led to the identification of 4-pyrroldino-2-(pyridin-2-yl) pyrimidine compound 1 as an RANKL-induced osteoclastogenesis inhibitor. The compound 1 showed high clearance values in microsomes, however. Modification of the pyrrolidino group to a benzylamino group improved human microsomal stability with a slight loss of in vitro activity. Substitution at the ortho position of the benzyl group ameliorated in vitro activity, and further fluorination of the benzyl group improved microsomal stability in rodents. Representative members of this series, compounds 20 and 23, exhibited efficacy in RANKL-induced osteopenic mice when administered orally at 0.3 mg/kg. (C) 2012 Elsevier Ltd. All rights reserved.