N-[3-[[4-(4-fluorophenyl)phenyl]methoxy]phenyl]-1-propan-2-ylpiperidine-4-carboxamide | 1277239-96-9

• 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: N-[3-[[4-(4-fluorophenyl)phenyl]methoxy]phenyl]-1-propan-2-ylpiperidine-4-carboxamide
• CAS: 1277239-96-9
• 化学式: C₂₈H₃₁FN₂O₂
• 分子量: 446.565
• InChiKey: PEZUZJNVAHSXOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[3-[[4-(4-fluorophenyl)phenyl]methoxy]phenyl]-1-propan-2-ylpiperidine-4-carboxamide 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以0.16 g的产率得到N-{3-[(4'-fluoro-1,1'-biphenyl-4-yl)methoxy]phenyl}-1-(1-methylethyl)piperidine-4-carboxamide hydrochloride
  参考文献：
  名称：

  Biarylmethoxy isonipecotanilides as potent and selective inhibitors of blood coagulation factor Xa

  摘要：

  New chloro-substituted biarylmethoxyphenyl piperidine-4-carboxamides were synthesized and assayed in vitro as inhibitors of the blood coagulation enzymes factor Xa (fXa) and thrombin. An investigation of effects of the amidine and isopropyl groups attached at the piperidine nitrogen and 5-(halogenoaryl)isoxazol-3-yl groups as biaryl substituents led us to identify new compounds which proved to be selective fXa inhibitors, with inhibition constants in the low nanomolar range. The most potent compound 21e, that incorporates 2-Cl-thiophen-5-yl group as the P1 motif and 1-isopropylpiperidine P4 group, inhibited fXa with K-i value of 0.3 nM and very high selectivity over thrombin and some other tested serine proteases, achieving moderate levels of anticoagulant activity in the low micromolar range, as assessed by the prothrombin time clotting assay (PT2 = 3.30 mu M). Based on reliable docking simulations, molecular modeling provided a rationale for interpreting structure-activity relationships. The predicted binding modes highlighted the structural requirements for addressing the subsites S1 and S4 of the fXa enzyme. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2010.11.010
• 作为产物：
  描述：

  4-氟苯硼酸 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 四丁基溴化铵 、 palladium diacetate 、 sodium hydride 、 sodium cyanoborohydride 、 potassium carbonate 作用下， 以 甲醇 、 四氯化碳 、 PEG₄₀₀ 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.75h， 生成 N-[3-[[4-(4-fluorophenyl)phenyl]methoxy]phenyl]-1-propan-2-ylpiperidine-4-carboxamide
  参考文献：
  名称：

  Biarylmethoxy isonipecotanilides as potent and selective inhibitors of blood coagulation factor Xa

  摘要：

  New chloro-substituted biarylmethoxyphenyl piperidine-4-carboxamides were synthesized and assayed in vitro as inhibitors of the blood coagulation enzymes factor Xa (fXa) and thrombin. An investigation of effects of the amidine and isopropyl groups attached at the piperidine nitrogen and 5-(halogenoaryl)isoxazol-3-yl groups as biaryl substituents led us to identify new compounds which proved to be selective fXa inhibitors, with inhibition constants in the low nanomolar range. The most potent compound 21e, that incorporates 2-Cl-thiophen-5-yl group as the P1 motif and 1-isopropylpiperidine P4 group, inhibited fXa with K-i value of 0.3 nM and very high selectivity over thrombin and some other tested serine proteases, achieving moderate levels of anticoagulant activity in the low micromolar range, as assessed by the prothrombin time clotting assay (PT2 = 3.30 mu M). Based on reliable docking simulations, molecular modeling provided a rationale for interpreting structure-activity relationships. The predicted binding modes highlighted the structural requirements for addressing the subsites S1 and S4 of the fXa enzyme. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2010.11.010