1-[6-(4-Fluoro-phenoxy)-pyridin-3-yl]-1,7,9-triaza-spiro[4.5]decane-6,8,10-trione | 959985-22-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[6-(4-Fluoro-phenoxy)-pyridin-3-yl]-1,7,9-triaza-spiro[4.5]decane-6,8,10-trione
• 英文别名: 1-[6-(4-fluorophenoxy)pyridin-3-yl]-1,7,9-triazaspiro[4.5]decane-6,8,10-trione
• CAS: 959985-22-9
• 化学式: C₁₈H₁₅FN₄O₄
• 分子量: 370.34
• InChiKey: AOSUTMRBALZLRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  diethyl 1-(6-(4-fluorophenoxy)pyridin-3-yl)pyrrolidine-2,2-dicarboxylate 、 尿素 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 以73%的产率得到1-[6-(4-Fluoro-phenoxy)-pyridin-3-yl]-1,7,9-triaza-spiro[4.5]decane-6,8,10-trione
  参考文献：
  名称：

  Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13

  摘要：

  Explorations in the pyrimidinetrione series of MMP-13 inhibitors led to the discovery of a series of spiro-fused compounds that are potent and selective inhibitiors of MMP-13. While other spiro-fused motifs are hydrolytically unstable, presumably due to electronic destabilization of the pyrimidinetrione ring, the spiropyrrolidine series does not share this liability. Greater than 100-fold selectivity versus other MMP family members was achieved by incorporation of an extended aryl-heteroaryl P1' group. When dosed as the sodium salt, these compounds displayed excellent oral absorption and pharmacokinetic properties. Despite the selectivity, a representative of this series produced fibroplasia in a 14 day rat study. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.09.085

文献信息

• Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors
  申请人：——

  公开号：US20030096803A1

  公开（公告）日：2003-05-22

  The present invention relates to 5-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors of the formula 1 wherein said “A” is a 5-7 membered heterocyclic ring as defined in the specification and to pharmaceutical compositions and methods of treating inflammation, cancer and other disorders.

  本发明涉及公式1中的5-螺环嘧啶-2,4,6-三酮金属蛋白酶抑制剂，其中“A”是在说明书中定义的5-7成员杂环。本发明还涉及制备药物组合物和治疗炎症、癌症和其他疾病的方法。
• SPIRO-PYRIMIDINE-2,4,6-TRIONE METALLOPROTEINASE INHIBITORS
  申请人：Pfizer Products Inc.

  公开号：EP1332146A2

  公开（公告）日：2003-08-06
• US6841671B2
  申请人：——

  公开号：US6841671B2

  公开（公告）日：2005-01-11
• [EN] SPIRO-PYRIMIDINE-2,4,6-TRIONE METALLOPROTEINASE INHIBITORS<br/>[FR] INHIBITEURS DE METALLOPROTEINASE SPIRO-PYRIMIDINE-2,4,6-TRIONE
  申请人：PFIZER PROD INC

  公开号：WO2002034753A2

  公开（公告）日：2002-05-02

  The present invention relates to 5-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors of the formula wherein said 'A' is a 5-7 membered heterocyclic ring as defined in the specification and to pharmaceutical compositions and methods of treating inflammation, cancer and othter disorders.