5-[(1,3-Dioxoisoindol-2-yl)methyl]-2-[8-methoxy-2-(trifluoromethyl)quinolin-5-yl]-1,3-oxazole-4-carboxylic acid | 871018-32-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 5-[(1,3-Dioxoisoindol-2-yl)methyl]-2-[8-methoxy-2-(trifluoromethyl)quinolin-5-yl]-1,3-oxazole-4-carboxylic acid
• CAS: 871018-32-5
• 化学式: C₂₄H₁₄F₃N₃O₆
• 分子量: 497.387
• InChiKey: RTBVLFZKPBVOSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  5-[(1,3-Dioxoisoindol-2-yl)methyl]-2-[8-methoxy-2-(trifluoromethyl)quinolin-5-yl]-1,3-oxazole-4-carboxylic acid 在 氨 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Discovery of a highly potent series of oxazole-based phosphodiesterase 4 inhibitors

  摘要：

  Substituted quinolyl oxazoles were discovered as a novel and highly potent series of phosphodiesterase 4 (PDE4) inhibitors. Structure-activity relationship studies revealed that the oxazole core, with 4-carboxamide and 5-aminomethyl groups, is a novel PDE4 inhibitory pharmacophore. Selectivity profiles and in vivo biological activity are also reported. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.092
• 作为产物：
  描述：

  Methyl 5-[(1,3-dioxoisoindol-2-yl)methyl]-2-[8-methoxy-2-(trifluoromethyl)quinolin-5-yl]-1,3-oxazole-4-carboxylate 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以87%的产率得到5-[(1,3-Dioxoisoindol-2-yl)methyl]-2-[8-methoxy-2-(trifluoromethyl)quinolin-5-yl]-1,3-oxazole-4-carboxylic acid
  参考文献：
  名称：

  Discovery of a highly potent series of oxazole-based phosphodiesterase 4 inhibitors

  摘要：

  Substituted quinolyl oxazoles were discovered as a novel and highly potent series of phosphodiesterase 4 (PDE4) inhibitors. Structure-activity relationship studies revealed that the oxazole core, with 4-carboxamide and 5-aminomethyl groups, is a novel PDE4 inhibitory pharmacophore. Selectivity profiles and in vivo biological activity are also reported. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.092

文献信息

• [EN] SUBSTITUTED 2-QUINOLYL-OXAZOLES USEFUL AS PDE4 INHIBITORS<br/>[FR] 2-QUINOLYLE-OXAZOLES SUBSTITUÉS UTILES COMME INHIBITEURS DU PDE4
  申请人：SCHERING CORP

  公开号：WO2005116009A1

  公开（公告）日：2005-12-08

  The invention claims compounds of the: (formula I); wherein: (formula II) is a 5-membered heteroaryl; X is S or O; R1 is H, alkyl, cycloalkyl, cylcoalkylalkyl-, -CH2F, -CHF2, -CF3, -C(O)alkyl or -C(O)NR18R19; R3 and R4 H, alkyl, hydroxyalkyl or -C(O)Oalkyl; R5 and R6 are H, alkyl, hydroxyalkyl, alkoxyalkyl, mercaptoalkyl, -CH2F, -CHF2, -CF3, -C(O)OH or -C(O)Oalkyl; R7 is H, alkyl, alkenyl, hydroxyalkyl, cycloalkyl, alkoxyalkyl, aminoalkyl, (R17-phenyl)alkyl or -CH2-C(O)-O-alkyl; and R8 comprises alkyl, heteroaryl, phenyl or cycloalkyl, or heterocycloalkyl, all optionally substituted, or a cycloalkyl- or heterocycloalkyl-substituted amide; or R7 and R8 and the nitrogen to which they are attached together form an optionally substituted ring; and the remaining variables are as defined in the specification. Also claimed are pharmaceutical compositions, the use of the compounds as PDE4 inhibitors, and combinations with other actives.

  该发明声明了以下化合物：(化学式I)；其中：(化学式II)是一种5-成员杂环芳基；X为S或O；R1为H，烷基，环烷基，环烷基烷基，-CH2F，-CHF2，-CF3，-C(O)烷基或-C(O)NR18R19；R3和R4为H，烷基，羟基烷基或-C(O)O烷基；R5和R6为H，烷基，羟基烷基，烷氧基烷基，巯基烷基，-CH2F，-CHF2，-CF3，-C(O)OH或-C(O)O烷基；R7为H，烷基，烯基，羟基烷基，环烷基，烷氧基烷基，氨基烷基，(R17-苯基)烷基或-CH2-C(O)-O-烷基；R8包括烷基，杂环芳基，苯基或环烷基，或杂环烷基，均可选择性取代，或环烷基或杂环烷基取代的酰胺；或R7和R8及它们附着的氮一起形成一个可选择性取代的环；其余变量如规范中所定义。还声明了药物组合物，将这些化合物用作PDE4抑制剂，并与其他活性物质组合使用。
• Substituted 2-quinolyl-oxazoles useful as PDE4 inhibitors
  申请人：Schering Corporation

  公开号：EP1758883B1

  公开（公告）日：2011-11-02
• US7511062B2
  申请人：——

  公开号：US7511062B2

  公开（公告）日：2009-03-31
• Discovery of a highly potent series of oxazole-based phosphodiesterase 4 inhibitors
  作者：Rongze Kuang、Ho-Jane Shue、David J. Blythin、Neng-Yang Shih、Danlin Gu、Xiao Chen、John Schwerdt、Ling Lin、Pauline C. Ting、Xiaohong Zhu、Robert Aslanian、John J. Piwinski、Li Xiao、Daniel Prelusky、Ping Wu、Ji Zhang、Xiang Zhang、Chander S. Celly、Michael Minnicozzi、Motasim Billah、Peng Wang

  DOI：10.1016/j.bmcl.2007.06.092

  日期：2007.9

  Substituted quinolyl oxazoles were discovered as a novel and highly potent series of phosphodiesterase 4 (PDE4) inhibitors. Structure-activity relationship studies revealed that the oxazole core, with 4-carboxamide and 5-aminomethyl groups, is a novel PDE4 inhibitory pharmacophore. Selectivity profiles and in vivo biological activity are also reported. (c) 2007 Elsevier Ltd. All rights reserved.