4'-(bromomethyl)-3-chlorobiphenyl | 1247065-93-5

• 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: 4'-(bromomethyl)-3-chlorobiphenyl
• 英文别名: 1-(Bromomethyl)-4-(3-chlorophenyl)benzene
• CAS: 1247065-93-5
• 化学式: C₁₃H₁₀BrCl
• 分子量: 281.579
• InChiKey: YXILTSSVKMSCOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  4'-(bromomethyl)-3-chlorobiphenyl 在 盐酸 、 sodium hydride 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.75h， 生成 N-[3-[[4-(3-chlorophenyl)phenyl]methoxy]phenyl]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：

  3-氯-4'-甲基联苯 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 为溶剂， 反应 20.0h， 生成 4'-(bromomethyl)-3-chlorobiphenyl
  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

文献信息

• Structure-based design, synthesis, and biological evaluation of lipophilic-tailed monocationic inhibitors of neuronal nitric oxide synthase
  作者：Fengtian Xue、Jinwen Huang、Haitao Ji、Jianguo Fang、Huiying Li、Pavel Martásek、Linda J. Roman、Thomas L. Poulos、Richard B. Silverman

  DOI：10.1016/j.bmc.2010.06.074

  日期：2010.9

  series of monocationic compounds was designed on the basis of docking experiments using the crystal structures of 1a,b bound to nNOS. These compounds were synthesized and evaluated for their ability to inhibit neuronal nitric oxide synthase. Despite the excellent overlap of these compounds with 1a,b bound to nNOS, they exhibited low potency. This is because they bound in the nNOS active site in the normal

  神经元一氧化氮合酶（nNOS）的选择性抑制剂有潜力发展成新的神经退行性疾病疗法。最近，我们描述了基于顺式吡咯烷药效团的新型 nNOS 抑制剂（ 1a和1b ）的发现。这些化合物和相关化合物被发现具有较差的血脑屏障渗透性，可能是因为分子中含有碱性氮。在此，利用与nNOS结合的1a、b的晶体结构，在对接实验的基础上设计了一系列单阳离子化合物。合成并评估了这些化合物抑制神经元一氧化氮合酶的能力。尽管这些化合物与结合至 nNOS 的1a、b具有极好的重叠，但它们表现出较低的效力。这是因为它们以正常方向而不是计算机建模中使用的预期翻转方向结合在 nNOS 活性位点中。联苯或苯氧基苯基尾部无序，不能形成良好的蛋白质-配体相互作用。这些研究证明了侧链尾部和第二个碱性氨基的大小和刚性对于 nNOS 结合效率的重要性以及疏水尾部对于 nNOS 活性位点构象定向的重要性。
• Biarylmethoxy isonipecotanilides as potent and selective inhibitors of blood coagulation factor Xa
  作者：Gianfranco Lopopolo、Filomena Fiorella、Modesto de Candia、Orazio Nicolotti、Sophie Martel、Pierre-Alain Carrupt、Cosimo Altomare

  DOI：10.1016/j.ejps.2010.11.010

  日期：2011.2

  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.