4-(5-cyano-7-propan-2-yl-1,3-benzoxazol-2-yl)-N-[[4-[3-(trifluoromethyl)phenyl]cyclohex-3-en-1-yl]methyl]benzamide | 1093685-65-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(5-cyano-7-propan-2-yl-1,3-benzoxazol-2-yl)-N-[[4-[3-(trifluoromethyl)phenyl]cyclohex-3-en-1-yl]methyl]benzamide
• CAS: 1093685-65-4
• 化学式: C₃₂H₂₈F₃N₃O₂
• 分子量: 543.588
• InChiKey: VQJJRJFAZWGINS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  78.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(5-cyano-7-propan-2-yl-1,3-benzoxazol-2-yl)-N-[[4-[3-(trifluoromethyl)phenyl]cyclohex-3-en-1-yl]methyl]benzamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 cis-4-(5-cyano-7-isopropylbenzo[d]oxazol-2-yl)-N-((4-(3-(trifluoromethyl)phenyl)cyclohexyl)methyl)benzamide 、 cis-4-(5-cyano-7-isopropylbenzo[d]oxazol-2-yl)-N-((4-(3-(trifluoromethyl)phenyl)cyclohexyl)methyl)benzamide
  参考文献：
  名称：

  2-(4-Carbonylphenyl)benzoxazole inhibitors of CETP: Attenuation of hERG binding and improved HDLc-raising efficacy

  摘要：

  The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Efforts focused on finding suitable replacements for the central piperidine with the aim of reducing hERG binding: a main liability of our benchmark benzoxazole (1a). Replacement of the piperidine with a cyclohexyl group successfully attenuated hERG binding, but was accompanied by reduced in vivo efficacy. The approach of substituting a piperidine moiety with an oxazolidinone also attenuated hERG binding. Further refinement of this latter scaffold via SAR at the pyridine terminus and methyl branching on the oxazolidinone led to compounds 7e and 7f, which raised HDLc by 33 and 27 mg/dl, respectively, in our transgenic mouse PD model and without the hERG liability of previous series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.049
• 作为产物：
  描述：

  4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-[(4-oxocyclohexyl)methyl]benzamide 在 2,6-二甲基吡啶 、 dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) 、 potassium carbonate 作用下， 生成 4-(5-cyano-7-propan-2-yl-1,3-benzoxazol-2-yl)-N-[[4-[3-(trifluoromethyl)phenyl]cyclohex-3-en-1-yl]methyl]benzamide
  参考文献：
  名称：

  2-(4-Carbonylphenyl)benzoxazole inhibitors of CETP: Attenuation of hERG binding and improved HDLc-raising efficacy

  摘要：

  The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Efforts focused on finding suitable replacements for the central piperidine with the aim of reducing hERG binding: a main liability of our benchmark benzoxazole (1a). Replacement of the piperidine with a cyclohexyl group successfully attenuated hERG binding, but was accompanied by reduced in vivo efficacy. The approach of substituting a piperidine moiety with an oxazolidinone also attenuated hERG binding. Further refinement of this latter scaffold via SAR at the pyridine terminus and methyl branching on the oxazolidinone led to compounds 7e and 7f, which raised HDLc by 33 and 27 mg/dl, respectively, in our transgenic mouse PD model and without the hERG liability of previous series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.049

文献信息

• 2-(4-Carbonylphenyl)benzoxazole inhibitors of CETP: Attenuation of hERG binding and improved HDLc-raising efficacy
  作者：Ramzi F. Sweis、Julianne A. Hunt、Peter J. Sinclair、Ying Chen、Suzanne S. Eveland、Qiu Guo、Sheryl A. Hyland、Denise P. Milot、Anne-Marie Cumiskey、Melanie Latham、Raymond Rosa、Larry Peterson、Carl P. Sparrow、Matt S. Anderson

  DOI：10.1016/j.bmcl.2011.02.049

  日期：2011.5

  The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Efforts focused on finding suitable replacements for the central piperidine with the aim of reducing hERG binding: a main liability of our benchmark benzoxazole (1a). Replacement of the piperidine with a cyclohexyl group successfully attenuated hERG binding, but was accompanied by reduced in vivo efficacy. The approach of substituting a piperidine moiety with an oxazolidinone also attenuated hERG binding. Further refinement of this latter scaffold via SAR at the pyridine terminus and methyl branching on the oxazolidinone led to compounds 7e and 7f, which raised HDLc by 33 and 27 mg/dl, respectively, in our transgenic mouse PD model and without the hERG liability of previous series. (C) 2011 Elsevier Ltd. All rights reserved.