(S)-(+)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine | 1172617-46-7

• 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: (S)-(+)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine
• 英文别名: Triazolopyridazine, 17；3-(2,5-dimethoxyphenyl)-6-[4-methoxy-3-[(3S)-oxolan-3-yl]oxyphenyl]-[1,2,4]triazolo[4,3-b]pyridazine
• CAS: 1172617-46-7
• 化学式: C₂₄H₂₄N₄O₅
• 分子量: 448.478
• InChiKey: HQUIEUONYYTHEW-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  89.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (S)-(+)-4-methoxy-3-(tetrahydrofuran-3-yloxy)phenylboronic acid 、 6-chloro-3-(2',5'-dimethoxyphenyl)-[1,2,4]triazolo[4,3-b]pyridazine 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 乙二醇二甲醚 为溶剂， 反应 0.5h， 以35%的产率得到(S)-(+)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine
  参考文献：
  名称：

  [EN] PHOSPHODIESTERASE INHIBITORS
  [FR] INHIBITEURS DE PHOSPHODIESTÉRASE

  摘要：

  这项发明涉及到公式I的化合物，用于抑制磷酸二酯酶-4。

  公开号：

  WO2009089027A1

文献信息

• [EN] PHOSPHODIESTERASE INHIBITORS<br/>[FR] INHIBITEURS DE PHOSPHODIESTÉRASE
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2009089027A1

  公开（公告）日：2009-07-16

  The invention relates to compounds of formula I useful for inhibiting phosphodiesterase-4.

  这项发明涉及到公式I的化合物，用于抑制磷酸二酯酶-4。
• PHOSPHODIESTERASE INHIBITORS
  申请人：Thomas Craig J.

  公开号：US20110112079A1

  公开（公告）日：2011-05-12

  The invention related to compounds for formula I useful for inhibiting phosphodiesterase-4.

  该发明涉及公式I的化合物，用于抑制磷酸二酯酶4。
• Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors
  作者：Amanda P. Skoumbourdis、Christopher A. LeClair、Eduard Stefan、Adrian G. Turjanski、William Maguire、Steven A. Titus、Ruili Huang、Douglas S. Auld、James Inglese、Christopher P. Austin、Stephen W. Michnick、Menghang Xia、Craig J. Thomas

  DOI：10.1016/j.bmcl.2009.01.057

  日期：2009.7

  An expansion of structure-activity studies on a series of substituted 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine PDE4 inhibitors and the introduction of a related [1,2,4]triazolo[4,3-b]pyridazine based inhibitor of PDE4 is presented. The development of SAR included strategic incorporation of known substituents on the critical catachol diether moiety of the 6-phenyl appendage on each heterocyclic core. From these studies, (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (10) and (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine (18) were identified as highly potent PDE4A inhibitors. Each of these analogues was submitted across a panel of 21 PDE family members and was shown to be highly selective for PDE4 isoforms (PDE4A, PDE4B, PDE4C, PDE4D). Both 10 and 18 were then evaluated in divergent cell-based assays to assess their relevant use as probes of PDE4 activity. Finally, docking studies with selective ligands (including 10 and 18) were undertaken to better understand this chemotypes ability to bind and inhibit PDE4 selectively. (C) 2009 Published by Elsevier Ltd.