1-(6-{4-[4-(4-cyano-phenyl)-oxazol-2-yl]-phenoxy}-pyridin-3-yl)-pyrrolidine-2,2-dicarboxylic acid diethyl ester | 620971-45-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(6-{4-[4-(4-cyano-phenyl)-oxazol-2-yl]-phenoxy}-pyridin-3-yl)-pyrrolidine-2,2-dicarboxylic acid diethyl ester
• 英文别名: diethyl 1-[6-[4-[4-(4-cyanophenyl)-1,3-oxazol-2-yl]phenoxy]pyridin-3-yl]pyrrolidine-2,2-dicarboxylate
• CAS: 620971-45-1
• 化学式: C₃₁H₂₈N₄O₆
• 分子量: 552.587
• InChiKey: MUVJEHNRQDLSGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  128
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-(6-{4-[4-(4-cyano-phenyl)-oxazol-2-yl]-phenoxy}-pyridin-3-yl)-pyrrolidine-2,2-dicarboxylic acid diethyl ester 、 尿素 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 16.58h， 生成 4-(2-{4-[5-(6,8,10-Trioxo-1,7,9-triaza-spiro[4.5]dec-1-yl)-pyridin-2-yloxy]-phenyl}-oxazol-4-yl)-benzonitrile
  参考文献：
  名称：

  Triaryl-oxy-aryl-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors

  摘要：

  本发明涉及一种三芳基氧基芳基螺环嘧啶-2,4,6-三酮金属蛋白酶抑制剂，其化学式为1，其中所述的环X为5-7成员杂环，且其中A、Y、B、G和W如规范中定义；以及用于治疗炎症、癌症和其他疾病的药物组合物和方法。

  公开号：

  US20030225056A1
• 作为产物：
  描述：

  4-(oxazol-4-yl)benzonitrile 、 diethyl 1-(6-(4-iodophenoxy)pyridin-3-yl)pyrrolidine-2,2-dicarboxylate 在 Pd-catalyst 正丁基锂 、 锌 作用下， 生成 1-(6-{4-[4-(4-cyano-phenyl)-oxazol-2-yl]-phenoxy}-pyridin-3-yl)-pyrrolidine-2,2-dicarboxylic acid diethyl ester
  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

• Triaryl-oxy-aryl-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors
  申请人：Pfizer Inc.

  公开号：US20030225056A1

  公开（公告）日：2003-12-04

  The present invention relates to triaryl-oxy-aryl-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors of the formula 1 wherein said ring X is a 5-7 membered heterocyclic ring, and wherein A, Y, B, G, and W are as defined in the specification; and to pharmaceutical compositions and methods of treating inflammation, cancer and other disorders.

  本发明涉及一种三芳基氧基芳基螺环嘧啶-2,4,6-三酮金属蛋白酶抑制剂，其化学式为1，其中所述的环X为5-7成员杂环，且其中A、Y、B、G和W如规范中定义；以及用于治疗炎症、癌症和其他疾病的药物组合物和方法。
• TRIARYL-OXY-ARYL-SPIRO-PYRIMIDINE-2, 4, 6-TRIONE METALLOPROTEINASE INHIBITORS
  申请人：Pfizer Products Inc.

  公开号：EP1501834B1

  公开（公告）日：2005-09-07
• US6916807B2
  申请人：——

  公开号：US6916807B2

  公开（公告）日：2005-07-12
• [EN] TRIARYL-OXY-ARYL-SPIRO-PYRIMIDINE-2, 4, 6-TRIONE METALLOPROTEINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA TRIARYL-OXY-ARYL-SPIRO-PYRIMIDINE-2, 4, 6-TRIONE METALLOPROTEINASE
  申请人：PFIZER PROD INC

  公开号：WO2003091259A1

  公开（公告）日：2003-11-06

  The present invention relates to triaryl-oxy-aryl-spiro-pyrimidine-2, 4, 6-trione metalloproteinase inhibitors of the formula (I) wherein said ring X is a 5-7 membered heterocyclic ring, and wherein A, Y, B, G and W are as defined in the specification; and to pharmaceutical compositions and methods of treating inflammation, cancer and other 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.