(E)-N-4-fluorobenzylpyrrole-2-carboaldehyde O-benzoyloxime

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-N-4-fluorobenzylpyrrole-2-carboaldehyde O-benzoyloxime
• 英文别名: [(E)-[1-[(4-fluorophenyl)methyl]pyrrol-2-yl]methylideneamino] benzoate
• 化学式: C₁₉H₁₅FN₂O₂
• 分子量: 322.339
• InChiKey: AEDGOSPQMWRUFB-FYJGNVAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-fluorobenzyl)-1H-pyrrole-2-carboxaldehyde 在 羟胺 、 sodium carbonate 作用下， 生成 (E)-N-4-fluorobenzylpyrrole-2-carboaldehyde O-benzoyloxime
  参考文献：
  名称：

  Potent inhibitors of lipoprotein-associated phospholipase A2: Benzaldehyde O-heterocycle-4-carbonyloxime

  摘要：

  A series of multi-substituted oximes were prepared and their potencies for inhibiting-lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity were evaluated in vitro. Among them, compounds 3a, 3b, and 3m were identified to display a micromolar potency for inhibiting Lp-PLA(2) in whole human plasma and isolated human LDL. Based on these results, structure-activity relationship was studied on modification of three parts of R-1, R-2, and R-3 to identify a potent pharmacophore for Lp-PLA(2). In an attempt to introduce various functional groups at R-2 and R-3, we discovered that replacement of less lipophilic groups led to an increase of inhibitory activity. Among the tested oxime derivatives, cyano- and morpholino-substituted analogue 4f at R-2 and R-3 had the highest potency with an IC50 value of 0.05 mu M in whole human plasma. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.08.031

文献信息

• NOVEL O-ACYLOXIME DERIVATIVES, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME FOR PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASE
  申请人：JEONG Tae-Sook

  公开号：US20060106017A1

  公开（公告）日：2006-05-18

  The present invention relates to novel O-acyloxime derivatives, a preparation method thereof and a pharmaceutical composition comprising the same for prevention and treatment of cardiovascular disease. The O-acyloxime derivatives according to the present invention may valuably be used for prevention and treatment of cardiovascular diseases such as hyperlipidemia, coronary arterial heart disease, atherosclerosis, and myocardial infarction caused by Lp-PLA 2 , because they have excellent inhibitory effect of Lp-PLA 2 .

  本发明涉及新型O-酰氧肟衍生物，其制备方法以及包含相同的用于预防和治疗心血管疾病的药物组合物。根据本发明的O-酰氧肟衍生物可以用于预防和治疗高脂血症、冠状动脉心脏病、动脉粥样硬化和由Lp-PLA2引起的心肌梗死等心血管疾病，因为它们具有优秀的抑制Lp-PLA2的作用。
• US7642291B2
  申请人：——

  公开号：US7642291B2

  公开（公告）日：2010-01-05
• US8399662B2
  申请人：——

  公开号：US8399662B2

  公开（公告）日：2013-03-19
• Potent inhibitors of lipoprotein-associated phospholipase A2: Benzaldehyde O-heterocycle-4-carbonyloxime
  作者：Hyung Jae Jeong、Yong-Dae Park、Ho-Yong Park、Il Yun Jeong、Tae-Sook Jeong、Woo Song Lee

  DOI：10.1016/j.bmcl.2006.08.031

  日期：2006.11

  A series of multi-substituted oximes were prepared and their potencies for inhibiting-lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity were evaluated in vitro. Among them, compounds 3a, 3b, and 3m were identified to display a micromolar potency for inhibiting Lp-PLA(2) in whole human plasma and isolated human LDL. Based on these results, structure-activity relationship was studied on modification of three parts of R-1, R-2, and R-3 to identify a potent pharmacophore for Lp-PLA(2). In an attempt to introduce various functional groups at R-2 and R-3, we discovered that replacement of less lipophilic groups led to an increase of inhibitory activity. Among the tested oxime derivatives, cyano- and morpholino-substituted analogue 4f at R-2 and R-3 had the highest potency with an IC50 value of 0.05 mu M in whole human plasma. (c) 2006 Elsevier Ltd. All rights reserved.