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.
• Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13
  作者：Kevin D. Freeman-Cook、Lawrence A. Reiter、Mark C. Noe、Amy S. Antipas、Dennis E. Danley、Kaushik Datta、James T. Downs、Shane Eisenbeis、James D. Eskra、David J. Garmene、Elaine M. Greer、Richard J. Griffiths、Roberto Guzman、Joel R. Hardink、Fouad Janat、Christopher S. Jones、Gary J. Martinelli、Peter G. Mitchell、Ellen R. Laird、Jennifer L. Liras、Lori L. Lopresti-Morrow、Jayvardhan Pandit、Usa D. Reilly、Donald Robertson、Marcie L. Vaughn-Bowser、Lilli A. Wolf-Gouviea、Sue A. Yocum

  DOI：10.1016/j.bmcl.2007.09.085

  日期：2007.12

  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.