2-(Dimethylamino)ethyl 4-(4-piperidin-4-ylphenyl)-7-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxylate | 1315308-18-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 2-(Dimethylamino)ethyl 4-(4-piperidin-4-ylphenyl)-7-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxylate
• CAS: 1315308-18-9
• 化学式: C₃₃H₃₃F₃N₂O₂
• 分子量: 546.632
• InChiKey: QRWSUKMIWRJHKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl 4-(4-(piperidin-4-yl)phenyl)-7-(4-(trifluoromethyl)phenyl)-2-naphthoate 在 甲醇 、 sodium carbonate 、 potassium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(Dimethylamino)ethyl 4-(4-piperidin-4-ylphenyl)-7-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxylate
  参考文献：
  名称：

  Applying the pro-drug approach to afford highly bioavailable antagonists of P2Y14

  摘要：

  Our series of competitive antagonists against the G-protein coupled receptor P2Y(14) were found to be highly shifted in the presence of serum (>99% protein bound). A binding assay using 2% human serum albumin (HSA) was developed to guide further SAR studies and led to the identification of the zwitterion 2, which is substantially less shifted (18-fold) than our previous lead compound 1 (323-fold). However, as the bioavailability of 2 was low, a library of ester pro-drugs was prepared (7a-7j) and assessed in vitro. The most interesting candidates were then profiled in vivo and led to the identification of the pro-drug 7j, which possesses a substantially improved pharmacokinetic profile. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.12.113

文献信息

• Applying the pro-drug approach to afford highly bioavailable antagonists of P2Y14
  作者：Joël Robichaud、Jean-François Fournier、Sébastien Gagné、Jacques Yves Gauthier、Martine Hamel、Yongxin Han、Martin Hénault、Stacia Kargman、Jean-François Levesque、Yaël Mamane、Joseph Mancini、Nicolas Morin、Erin Mulrooney、Jin Wu、W. Cameron Black

  DOI：10.1016/j.bmcl.2010.12.113

  日期：2011.7

  Our series of competitive antagonists against the G-protein coupled receptor P2Y(14) were found to be highly shifted in the presence of serum (>99% protein bound). A binding assay using 2% human serum albumin (HSA) was developed to guide further SAR studies and led to the identification of the zwitterion 2, which is substantially less shifted (18-fold) than our previous lead compound 1 (323-fold). However, as the bioavailability of 2 was low, a library of ester pro-drugs was prepared (7a-7j) and assessed in vitro. The most interesting candidates were then profiled in vivo and led to the identification of the pro-drug 7j, which possesses a substantially improved pharmacokinetic profile. (C) 2011 Published by Elsevier Ltd.