methyl (4-(2-chlorophenyl)-2-{4-[2-(1H-pyrazol-4-yl)ethoxy]phenyl}thien-3-yl)acetate | 905838-80-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl (4-(2-chlorophenyl)-2-{4-[2-(1H-pyrazol-4-yl)ethoxy]phenyl}thien-3-yl)acetate
• 英文别名: methyl 2-[4-(2-chlorophenyl)-2-[4-[2-(1H-pyrazol-4-yl)ethoxy]phenyl]thiophen-3-yl]acetate
• CAS: 905838-80-4
• 化学式: C₂₄H₂₁ClN₂O₃S
• 分子量: 452.961
• InChiKey: RRSMLZBYLSBSEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (4-(2-chlorophenyl)-2-{4-[2-(1H-pyrazol-4-yl)ethoxy]phenyl}thien-3-yl)acetate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以95%的产率得到2-[4-(2-chlorophenyl)-2-[4-[2-(1H-pyrazol-4-yl)ethoxy]phenyl]thiophen-3-yl]acetic acid
  参考文献：
  名称：

  Thiophene substituted acylguanidines as BACE1 inhibitors

  摘要：

  A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay.

  DOI：

  10.1016/j.bmcl.2007.08.010
• 作为产物：
  描述：

  methyl 2-(2-(4-(2-(1H-pyrazol-4-yl)ethoxy)phenyl)-4-bromothiophen-3-yl)acetate 、 2-氯苯基硼酸 在 palladium bis[bis(diphenylphosphino)ferrocene] dichloride potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 生成 methyl (4-(2-chlorophenyl)-2-{4-[2-(1H-pyrazol-4-yl)ethoxy]phenyl}thien-3-yl)acetate
  参考文献：
  名称：

  Thiophene substituted acylguanidines as BACE1 inhibitors

  摘要：

  A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay.

  DOI：

  10.1016/j.bmcl.2007.08.010

文献信息

• Substituted thienyl and furyl acylguanidines and methods of their use as beta-secretase modulators
  申请人：Fobare Floyd William

  公开号：US20060183792A1

  公开（公告）日：2006-08-17

  The present invention provides a substituted thienyl or furyl acylguanidine compound of formula I The present invention also provides methods for the inhibition of β-secretase (BACE) and for the treatment of β-amyloid deposits and neurofibrillary tangles.

  本发明提供了一种式I的取代噻吩或呋喃酰基胍化合物。 本发明还提供了用于抑制β-分泌酶（BACE）和治疗β-淀粉样沉积物和神经原纤维缠结的方法。
• Thiophene substituted acylguanidines as BACE1 inhibitors
  作者：William F. Fobare、William R. Solvibile、Albert J. Robichaud、Michael S. Malamas、Eric Manas、Jim Turner、Yun Hu、Erik Wagner、Rajiv Chopra、Rebecca Cowling、Guixan Jin、Jonathan Bard

  DOI：10.1016/j.bmcl.2007.08.010

  日期：2007.10

  A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay.