N¹-(2-chlorophenyl)-N²-(4-methoxy-2-((4-(3-oxomorpholino)phenyl)carbamoyl)phenyl)oxalamide

• 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: N¹-(2-chlorophenyl)-N²-(4-methoxy-2-((4-(3-oxomorpholino)phenyl)carbamoyl)phenyl)oxalamide
• 英文别名: N'-(2-chlorophenyl)-N-[4-methoxy-2-[[4-(3-oxomorpholin-4-yl)phenyl]carbamoyl]phenyl]oxamide
• 化学式: C₂₆H₂₃ClN₄O₆
• 分子量: 522.945
• InChiKey: DBTJJCVRJNGSRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-苯基-3-吗啉酮 在 4-二甲氨基吡啶 、 硫酸 、 palladium 10% on activated carbon 、 硝酸 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 142.0h， 生成 N¹-(2-chlorophenyl)-N²-(4-methoxy-2-((4-(3-oxomorpholino)phenyl)carbamoyl)phenyl)oxalamide
  参考文献：
  名称：

  Identification of anthranilamide derivatives as potential factor Xa inhibitors: Drug design, synthesis and biological evaluation

  摘要：

  The coagulation enzyme factor Xa (Ma) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel Ma inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against Ma. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 mu M). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 x PT value of 8.7 mu M. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.052

文献信息

• Identification of anthranilamide derivatives as potential factor Xa inhibitors: Drug design, synthesis and biological evaluation
  作者：Junhao Xing、Lingyun Yang、Hui Li、Qing Li、Leilei Zhao、Xinning Wang、Yuan Zhang、Muxing Zhou、Jinpei Zhou、Huibin Zhang

  DOI：10.1016/j.ejmech.2015.03.052

  日期：2015.5

  The coagulation enzyme factor Xa (Ma) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel Ma inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against Ma. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 mu M). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 x PT value of 8.7 mu M. (C) 2015 Elsevier Masson SAS. All rights reserved.