4-[(2R)-1-oxo-1-{[4-(trifluoromethyl)-1,3-oxazol-2-yl]amino}propan-2-yl]phenyl trifluoromethanesulfonate | 1330128-62-5

• 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: 4-[(2R)-1-oxo-1-{[4-(trifluoromethyl)-1,3-oxazol-2-yl]amino}propan-2-yl]phenyl trifluoromethanesulfonate
• 英文别名: [4-[(2R)-1-oxo-1-[[4-(trifluoromethyl)-1,3-oxazol-2-yl]amino]propan-2-yl]phenyl] trifluoromethanesulfonate
• CAS: 1330128-62-5
• 化学式: C₁₄H₁₀F₆N₂O₅S
• 分子量: 432.3
• InChiKey: KJBYDWUCMDJJRD-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  (R)-2-[4-[(三氟甲基磺酰基)氧基]苯基]丙酸 、 2-氨基-4-(三氟甲基)恶唑 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 以37%的产率得到4-[(2R)-1-oxo-1-{[4-(trifluoromethyl)-1,3-oxazol-2-yl]amino}propan-2-yl]phenyl trifluoromethanesulfonate
  参考文献：
  名称：

  Aryltriflates as a Neglected Moiety in Medicinal Chemistry: A Case Study from a Lead Optimization of CXCL8 Inhibitors

  摘要：

  Interleukin-8 and growth related oncogene-alpha-chemokines (formerly CXCL8 and CXCL1, respectively) mediate chemotaxis of neutrophils to inflammatory sites via interactions with two transmembrane receptors, the type A CXCL8 receptor (CXCR1) and the type B CXCL8 receptor (CXCR2). In a previous work, we published the molecular modeling-driven structure activity relationship (SAR) results culminated in the discovery of R-(-)-2-[(4'-trifluoromethanesulphonyloxy) phenyl]-N-methanesulfonyl propionamide (19), in which an unusual aryltriflate moiety was embedded. Although triflates are broadly used in organic synthesis, this group is scarcely used in medicinal chemistry programs. Here we detail the drug profiling-driven approach used for the selection and characterization of 19, the most potent dual CXCR1 and CXCR2 noncompetitive inhibitor described to date. Reported data suggest that the aryltriflate moiety might represent a valid choice for the selection of clinical candidates with suitable druglike properties.

  DOI：

  10.1021/ml2001533

文献信息

• Aryltriflates as a Neglected Moiety in Medicinal Chemistry: A Case Study from a Lead Optimization of CXCL8 Inhibitors
  作者：Alessio Moriconi、Chiara Bigogno、Gianluca Bianchini、Antonio Caligiuri、Anna Resconi、Massimo G. Dondio、Gaetano D’Anniballe、Marcello Allegretti

  DOI：10.1021/ml2001533

  日期：2011.10.13

  Interleukin-8 and growth related oncogene-alpha-chemokines (formerly CXCL8 and CXCL1, respectively) mediate chemotaxis of neutrophils to inflammatory sites via interactions with two transmembrane receptors, the type A CXCL8 receptor (CXCR1) and the type B CXCL8 receptor (CXCR2). In a previous work, we published the molecular modeling-driven structure activity relationship (SAR) results culminated in the discovery of R-(-)-2-[(4'-trifluoromethanesulphonyloxy) phenyl]-N-methanesulfonyl propionamide (19), in which an unusual aryltriflate moiety was embedded. Although triflates are broadly used in organic synthesis, this group is scarcely used in medicinal chemistry programs. Here we detail the drug profiling-driven approach used for the selection and characterization of 19, the most potent dual CXCR1 and CXCR2 noncompetitive inhibitor described to date. Reported data suggest that the aryltriflate moiety might represent a valid choice for the selection of clinical candidates with suitable druglike properties.