tert-butyl 4-(4-oxo-4H-chromen-3-yl)benzoate | 1338224-04-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: tert-butyl 4-(4-oxo-4H-chromen-3-yl)benzoate
• 英文别名: Tert-butyl 4-(4-oxochromen-3-yl)benzoate
• CAS: 1338224-04-6
• 化学式: C₂₀H₁₈O₄
• 分子量: 322.361
• InChiKey: PCZDAQUDNUTQHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-oxo-4H-chromen-3-yl)benzoate 在 三氟乙酸 作用下， 反应 0.17h， 生成 4-(4-oxo-4H-chromen-3-yl)benzoic acid
  参考文献：
  名称：

  Discovery of Potent, Orally Bioavailable Phthalazinone Bradykinin B1 Receptor Antagonists

  摘要：

  The bradykinin B1 receptor is rapidly induced upon tissue injury and inflammation, stimulating the production of inflammatory mediators resulting in plasma extravasation, leukocyte trafficking, edema, and pain. We have previously reported on sulfonamide and sulfone-based B1 antagonists containing a privileged bicyclic amine moiety leading to potent series of 2-oxopiperazines. The suboptimal pharmacokinetics and physicochemical properties of the oxopiperazine sulfonamides led us to seek B1 antagonists with improved druglike properties. Using a pharmacophore model containing a bicyclic amine as anchor, we designed a series of amide antagonists with targeted physicochemical properties. This approach led to a novel series of potent phthalazinone B1 antagonists, where we successfully replaced a sulfonamide acceptor with a cyclic carbonyl unit. SAR studies revealed compounds with subnanomolar B1 binding affinity. These compounds demonstrate excellent cross-species PK properties with high oral bioavailability and potent activity in a rabbit biochemical challenge pharmacodynamic study.

  DOI：

  10.1021/jm200808v
• 作为产物：
  描述：

  4-(叔丁氧基羰基)苯硼酸 、 3-溴色酮 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.33h， 以42.4%的产率得到tert-butyl 4-(4-oxo-4H-chromen-3-yl)benzoate
  参考文献：
  名称：

  Discovery of Potent, Orally Bioavailable Phthalazinone Bradykinin B1 Receptor Antagonists

  摘要：

  The bradykinin B1 receptor is rapidly induced upon tissue injury and inflammation, stimulating the production of inflammatory mediators resulting in plasma extravasation, leukocyte trafficking, edema, and pain. We have previously reported on sulfonamide and sulfone-based B1 antagonists containing a privileged bicyclic amine moiety leading to potent series of 2-oxopiperazines. The suboptimal pharmacokinetics and physicochemical properties of the oxopiperazine sulfonamides led us to seek B1 antagonists with improved druglike properties. Using a pharmacophore model containing a bicyclic amine as anchor, we designed a series of amide antagonists with targeted physicochemical properties. This approach led to a novel series of potent phthalazinone B1 antagonists, where we successfully replaced a sulfonamide acceptor with a cyclic carbonyl unit. SAR studies revealed compounds with subnanomolar B1 binding affinity. These compounds demonstrate excellent cross-species PK properties with high oral bioavailability and potent activity in a rabbit biochemical challenge pharmacodynamic study.

  DOI：

  10.1021/jm200808v

文献信息

• Discovery of Potent, Orally Bioavailable Phthalazinone Bradykinin B1 Receptor Antagonists
  作者：Kaustav Biswas、Tanya A. N. Peterkin、Marian C. Bryan、Leyla Arik、Sonya G. Lehto、Hong Sun、Feng-Yin Hsieh、Cen Xu、Robert T. Fremeau、Jennifer R. Allen

  DOI：10.1021/jm200808v

  日期：2011.10.27

  The bradykinin B1 receptor is rapidly induced upon tissue injury and inflammation, stimulating the production of inflammatory mediators resulting in plasma extravasation, leukocyte trafficking, edema, and pain. We have previously reported on sulfonamide and sulfone-based B1 antagonists containing a privileged bicyclic amine moiety leading to potent series of 2-oxopiperazines. The suboptimal pharmacokinetics and physicochemical properties of the oxopiperazine sulfonamides led us to seek B1 antagonists with improved druglike properties. Using a pharmacophore model containing a bicyclic amine as anchor, we designed a series of amide antagonists with targeted physicochemical properties. This approach led to a novel series of potent phthalazinone B1 antagonists, where we successfully replaced a sulfonamide acceptor with a cyclic carbonyl unit. SAR studies revealed compounds with subnanomolar B1 binding affinity. These compounds demonstrate excellent cross-species PK properties with high oral bioavailability and potent activity in a rabbit biochemical challenge pharmacodynamic study.