(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 | 1257249-91-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: (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
• CAS: 1257249-91-4
• 化学式: C₂₄H₂₉FN₄
• 分子量: 392.519
• InChiKey: DKVUCJXNERTSTE-CBPXPLCBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.74
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  47.08
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  tert-butyl ((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)carbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以95%的产率得到(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
  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