IM 491 | 252918-63-1

• 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: IM 491
• 英文别名: N-3-hydroxy-1-methyl-N-2-[4-[(2-methyl-4-quinolinyl)methoxy]phenyl]-2(S),3(S)-piperidinedicarboxamide；2,3-Piperidinedicarboxamide, N3-hydroxy-1-methyl-N2-(4-((2-methyl-4-quinolinyl)methoxy)phenyl)-, (2S,3S)-；(2S,3S)-3-N-hydroxy-1-methyl-2-N-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]piperidine-2,3-dicarboxamide
• CAS: 252918-63-1
• 化学式: C₂₅H₂₈N₄O₄
• 分子量: 448.522
• InChiKey: RJSKOAOWDAMMHR-GMAHTHKFSA-N

物化性质

• 密度：
  1.298±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (2S,3S)-2-[4-(2-Methyl-quinolin-4-ylmethoxy)-phenylcarbamoyl]-piperidine-3-carboxylic acid tert-butyl ester 在 盐酸羟胺 、 三乙酰氧基硼氢化钠 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 IM 491
  参考文献：
  名称：

  Rational design, synthesis and structure–activity relationships of a cyclic succinate series of TNF-α converting enzyme inhibitors. Part 2: lead optimization

  摘要：

  Modifications of the lead TACE inhibitor 1 (N-hydroxy-trans-2-{[4-(4-quinolinyloxymethyl)anilinyl]carbonyl}-1-cyclo-hexanecarboxamide) at the cyclohexyl ring and the quinoline moiety led to the identification of a series of piperidine containing TACE inhibitors with potent activity in the inhibition of TNF-alpha release in the whole blood assay (WBA). The most potent analogue IM491 [N-hydroxy-(5S,6S)-1-methyl-6-{[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl}-5-piperidinecarboxamide] exhibited an IC50 value of 20 nM in WBA with excellent selectivity over MMP-1, -2 and -9 and is orally bioavailable with an F value of 43% in beagle dogs. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.057

文献信息

• Compounds and methods for improving platelet recovery and function
  申请人：Wagner D. Denisa

  公开号：US20050019743A1

  公开（公告）日：2005-01-27

  The present invention describes an improved blood product suitable for use in transfusions comprising, in combination, blood platelets and an inhibitor of platelet glycoprotein Ibα cleavage from platelets, such as a metalloproteinase inhibitor or a TACE inhibitor. Containers for storing the improved blood product for periods of up to about 10 days, and methods for testing and using the recovered improved blood product in patient transfusions, are also provided.

  本发明描述了一种适用于输血的改良血液制品，它由血小板和血小板糖蛋白Ⅰbα裂解抑制剂（如金属蛋白酶抑制剂或TACE抑制剂）组合而成。此外，还提供了可将改良血液制品储存 10 天左右的容器，以及在患者输血中检测和使用回收的改良血液制品的方法。
• Rational design, synthesis and structure–activity relationships of a cyclic succinate series of TNF-α converting enzyme inhibitors. Part 2: lead optimization
  作者：Chu-Biao Xue、Xiaohua He、John Roderick、Ronald L Corbett、James J.-W Duan、Rui-Qin Liu、Maryanne B Covington、Mingxin Qian、Maria D Ribadeneira、Krishna Vaddi、David D Christ、Robert C Newton、James M Trzaskos、Ronald L Magolda、Ruth R Wexler、Carl P Decicco

  DOI：10.1016/j.bmcl.2003.09.057

  日期：2003.12

  Modifications of the lead TACE inhibitor 1 (N-hydroxy-trans-2-[4-(4-quinolinyloxymethyl)anilinyl]carbonyl}-1-cyclo-hexanecarboxamide) at the cyclohexyl ring and the quinoline moiety led to the identification of a series of piperidine containing TACE inhibitors with potent activity in the inhibition of TNF-alpha release in the whole blood assay (WBA). The most potent analogue IM491 [N-hydroxy-(5S,6S)-1-methyl-6-[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl}-5-piperidinecarboxamide] exhibited an IC50 value of 20 nM in WBA with excellent selectivity over MMP-1, -2 and -9 and is orally bioavailable with an F value of 43% in beagle dogs. (C) 2003 Elsevier Ltd. All rights reserved.