6-chloro-4-(piperidin-3-ylmethoxy)-1-benzopyran-2-one trifluoroacetate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 6-chloro-4-(piperidin-3-ylmethoxy)-1-benzopyran-2-one trifluoroacetate
• 英文别名: 6-chloro-4-(piperidin-3-ylmethoxy)-1-benzopyran-2-one trifluoroacetic acid salt；6-Chloro-4-(piperidin-3-ylmethoxy)chromen-2-one;2,2,2-trifluoroacetic acid；6-chloro-4-(piperidin-3-ylmethoxy)chromen-2-one;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₁₅H₁₆ClNO₃
• 分子量: 407.774
• InChiKey: HIVWPFHSVLCPNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.46
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-Boc-3-羟甲基哌啶 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 6-chloro-4-(piperidin-3-ylmethoxy)-1-benzopyran-2-one trifluoroacetate
  参考文献：
  名称：

  Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase

  摘要：

  Inducible nitric oxide synthase (iNOS) has been implicated in various central and peripheral pathophysiological diseases. Our high throughput screening initially identified a weak inhibitor of iNOS, thiocoumarin 13. From this lead, a number of potent derivatives were prepared that demonstrate favorable potency, selectivity and kinetics. Compound 30 has an IC50 of 60 nM for mouse iNOS and 185-fold and 9-fold selectivity for bovine eNOS and rat nNOS, respectively. In cellular assays for iNOS, this compound has micromolar potency. Furthermore, two compounds (16 and 30) demonstrate a reasonable pharmacokinetic profile in rodents. The synthesis, SAR, and biological activity of this novel class of compounds is described.

  DOI：

  10.1016/j.bmc.2005.02.036

文献信息

• Coumarins as iNOS inhibitors
  申请人：Jackson Sharon

  公开号：US20050054681A1

  公开（公告）日：2005-03-10

  The present invention relates to coumarins of the formula (I): that are useful as inhibitors of nitric oxide synthase. Pharmaceutical compositions and methods of using these compounds as inhibitors of nitric oxide synthase are described herein.

  本发明涉及一种具有以下结构的香豆素（I）：这些化合物可作为一氧化氮合酶的抑制剂。本文描述了这些化合物作为一氧化氮合酶抑制剂的药物组合物和使用方法。
• [EN] COUMARINS AS INOS INHIBITORS<br/>[FR] COUMARINES COMME INHIBITEURS DE L'OXYDE NITRIQUE SYNTHASE INDUCTIBLE (INOS)
  申请人：AVENTIS PHARMA INC

  公开号：WO2005026143A1

  公开（公告）日：2005-03-24

  The present invention relates to coumarins of the Formula (1) : that are useful as inhibitors of nitric oxide synthase. Pharmaceutical compositions and methods of using these compounds as inhibitors of nitric oxide synthase are described herein.

  本发明涉及公式（1）的香豆素，其可用作一氧化氮合酶的抑制剂。本文描述了这些化合物作为一氧化氮合酶抑制剂的药物组合物和使用方法。
• COUMARINS AS INOS INHIBITORS
  申请人：AVENTIS PHARMACEUTICALS INC.

  公开号：EP1667988A1

  公开（公告）日：2006-06-14
• US7538233B2
  申请人：——

  公开号：US7538233B2

  公开（公告）日：2009-05-26
• Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase
  作者：Sharon A. Jackson、Sukhveen Sahni、Lan Lee、Yongyi Luo、Thaddeus R. Nieduzak、Guyan Liang、Yulin Chiang、Nicola Collar、David Fink、Wei He、Abdelazize Laoui、Jean Merrill、Ray Boffey、Peter Crackett、Bryan Rees、Melanie Wong、Jean-Pierre Guilloteau、Magali Mathieu、Sam S. Rebello

  DOI：10.1016/j.bmc.2005.02.036

  日期：2005.4

  Inducible nitric oxide synthase (iNOS) has been implicated in various central and peripheral pathophysiological diseases. Our high throughput screening initially identified a weak inhibitor of iNOS, thiocoumarin 13. From this lead, a number of potent derivatives were prepared that demonstrate favorable potency, selectivity and kinetics. Compound 30 has an IC50 of 60 nM for mouse iNOS and 185-fold and 9-fold selectivity for bovine eNOS and rat nNOS, respectively. In cellular assays for iNOS, this compound has micromolar potency. Furthermore, two compounds (16 and 30) demonstrate a reasonable pharmacokinetic profile in rodents. The synthesis, SAR, and biological activity of this novel class of compounds is described.