N-((S)-1-(3-fluorophenyl)-3-((1R,3S,5S)-3-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)propyl)tetrahydro-2H-thiopyran-4-carboxamide | 1257249-79-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: N-((S)-1-(3-fluorophenyl)-3-((1R,3S,5S)-3-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)propyl)tetrahydro-2H-thiopyran-4-carboxamide
• CAS: 1257249-79-8
• 化学式: C₃₀H₃₇FN₄OS
• 分子量: 520.714
• InChiKey: VFCFLBJGQGUVFG-YAOOYPAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.04
• 重原子数：
  37.0
• 可旋转键数：
  7.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  50.16
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-((S)-1-(3-fluorophenyl)-3-((1R,3S,5S)-3-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)propyl)tetrahydro-2H-thiopyran-4-carboxamide 在 双氧水 作用下， 以 水 为溶剂， 以77%的产率得到N-((S)-1-(3-fluorophenyl)-3-((1R,3S,5S)-3-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)propyl)tetrahydro-2H-thiopyran-4-carboxamide 1,1-dioxide
  参考文献：
  名称：

  An in situ oxidation strategy towards overcoming hERG affinity

  摘要：

  In an effort to overcome hERG affinity with a lead compound, several S-oxide and N-oxide analogues were synthesised with a much improved hERG profile but low in vivo absorption. This led to the implementation of an in situ oxidation strategy wherein a sulfide was dosed orally and systemic levels of the corresponding sulfoxide and sulfone were monitored. SAR and pharmacokinetic data to support this as a possible strategy are presented, although ultimately the approach was shown not to be suitable due to very low levels of active circulating metabolites. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.089
• 作为产物：
  描述：

  四氢-(9ci)-2H-硫代吡喃-4-羧酸 、 (S)-1-(3-fluorophenyl)-3-((1R,3S,5S)-3-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)propan-1-amine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以65%的产率得到N-((S)-1-(3-fluorophenyl)-3-((1R,3S,5S)-3-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)propyl)tetrahydro-2H-thiopyran-4-carboxamide
  参考文献：
  名称：

  An in situ oxidation strategy towards overcoming hERG affinity

  摘要：

  In an effort to overcome hERG affinity with a lead compound, several S-oxide and N-oxide analogues were synthesised with a much improved hERG profile but low in vivo absorption. This led to the implementation of an in situ oxidation strategy wherein a sulfide was dosed orally and systemic levels of the corresponding sulfoxide and sulfone were monitored. SAR and pharmacokinetic data to support this as a possible strategy are presented, although ultimately the approach was shown not to be suitable due to very low levels of active circulating metabolites. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.089