3-fluoro-2'-(piperidin-1-ylsulfonyl)biphenyl-4-carbaldehyde | 1322001-36-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-fluoro-2'-(piperidin-1-ylsulfonyl)biphenyl-4-carbaldehyde
• 英文别名: [1,1a(2)-Biphenyl]-4-carboxaldehyde, 3-fluoro-2a(2)-(1-piperidinylsulfonyl)-；2-fluoro-4-(2-piperidin-1-ylsulfonylphenyl)benzaldehyde
• CAS: 1322001-36-4
• 化学式: C₁₈H₁₈FNO₃S
• 分子量: 347.41
• InChiKey: SNYSJUOKFZXOFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  62.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-哌啶乙醇 、 3-fluoro-2'-(piperidin-1-ylsulfonyl)biphenyl-4-carbaldehyde 在 三乙酰氧基硼氢化钠 、 盐酸 作用下， 以 二氯甲烷 、 乙醚 、 水 为溶剂， 反应 0.5h， 以45%的产率得到2-(1-((3-fluoro-2'-(piperidin-1-ylsulfonyl)biphenyl-4-yl)methyl)piperidin-4-yl)ethanol
  参考文献：
  名称：

  Design and Discovery of a Selective Small Molecule κ Opioid Antagonist (2-Methyl-N-((2′-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242)

  摘要：

  By use of parallel chemistry coupled with physicochemical property design, a series of selective kappa opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro kappa antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure-response relationship between the kappa K-i and the free brain drug levels. This strategy identified 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242, which entered phase 1 clinical testing and has demonstrated target engagement in healthy volunteers.

  DOI：

  10.1021/jm2006035
• 作为产物：
  描述：

  2-溴苯磺酰氯 在 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 sodium carbonate 、 三乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 3-fluoro-2'-(piperidin-1-ylsulfonyl)biphenyl-4-carbaldehyde
  参考文献：
  名称：

  Design and Discovery of a Selective Small Molecule κ Opioid Antagonist (2-Methyl-N-((2′-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242)

  摘要：

  By use of parallel chemistry coupled with physicochemical property design, a series of selective kappa opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro kappa antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure-response relationship between the kappa K-i and the free brain drug levels. This strategy identified 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242, which entered phase 1 clinical testing and has demonstrated target engagement in healthy volunteers.

  DOI：

  10.1021/jm2006035

文献信息

• Design and Discovery of a Selective Small Molecule κ Opioid Antagonist (2-Methyl-<i>N</i>-((2′-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242)
  作者：Patrick R. Verhoest、Aarti Sawant Basak、Vinod Parikh、Matthew Hayward、Gregory W. Kauffman、Vanessa Paradis、Stanton F. McHardy、Stafford McLean、Sarah Grimwood、Anne W. Schmidt、Michelle Vanase-Frawley、Jodi Freeman、Jeffrey Van Deusen、Loretta Cox、Diane Wong、Spiros Liras

  DOI：10.1021/jm2006035

  日期：2011.8.25

  By use of parallel chemistry coupled with physicochemical property design, a series of selective kappa opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro kappa antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure-response relationship between the kappa K-i and the free brain drug levels. This strategy identified 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242, which entered phase 1 clinical testing and has demonstrated target engagement in healthy volunteers.