5-[3-(4-fluorophenyl)-7-[(5R)-5-(4-fluorophenyl)-5-methyl-4H-1,2-oxazol-3-yl]-4-oxoquinazolin-2-yl]pentanoic acid | 1373275-59-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-[3-(4-fluorophenyl)-7-[(5R)-5-(4-fluorophenyl)-5-methyl-4H-1,2-oxazol-3-yl]-4-oxoquinazolin-2-yl]pentanoic acid
• CAS: 1373275-59-2
• 化学式: C₂₉H₂₅F₂N₃O₄
• 分子量: 517.532
• InChiKey: CRSQAMAGSKEBHU-GDLZYMKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  91.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  甲基脂肪酰氯 在 三乙基硅烷 、 sodium hypochlorite 、 盐酸羟胺 、 sodium acetate 、 钯 、 三乙胺 、 lithium hydroxide 作用下， 生成 5-[3-(4-fluorophenyl)-7-[(5S)-5-(4-fluorophenyl)-5-methyl-4H-1,2-oxazol-3-yl]-4-oxoquinazolin-2-yl]pentanoic acid 、 5-[3-(4-fluorophenyl)-7-[(5R)-5-(4-fluorophenyl)-5-methyl-4H-1,2-oxazol-3-yl]-4-oxoquinazolin-2-yl]pentanoic acid
  参考文献：
  名称：

  Quality by design (QbD) of amide isosteres: 5,5-Disubstituted isoxazolines as potent CRTh2 antagonists with favorable pharmacokinetic and drug-like properties

  摘要：

  Isoxazoles are frequently used amide isosteres, as shown in the context of discovery of CRTh2 antagonists from amide 1 to isoxazole 2. However, persistent agonism and poor solubility in isoxazole series presented challenges to its further development. Based on the concept of quality by design (QbD), 5,5-disubstituted isoxazolines 3 were introduced. The chirality at 5 position of isoxazolines controlled the switch between two modes of actions, which led to a novel series of pure antagonists. This non-planar motif also conferred a change of shape of these molecules, which avoided flat structures and improved their physical properties. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.043

文献信息

• Quality by design (QbD) of amide isosteres: 5,5-Disubstituted isoxazolines as potent CRTh2 antagonists with favorable pharmacokinetic and drug-like properties
  作者：Dong Xiao、Xiaohong Zhu、Younong Yu、Ning Shao、Jie Wu、Kevin D. McCormick、Pawan Dhondi、Jun Qin、Robert Mazzola、Haiqun Tang、Ashwin Rao、Phieng Siliphaivanh、Hongchen Qiu、Xiaoxin Yang、Maria Rivelli、Charles G. Garlisi、Steve Eckel、Gitali Mukhopadhyay、Craig Correll、Diane Rindgen、Robert Aslanian、Anandan Palani

  DOI：10.1016/j.bmcl.2014.01.043

  日期：2014.3

  Isoxazoles are frequently used amide isosteres, as shown in the context of discovery of CRTh2 antagonists from amide 1 to isoxazole 2. However, persistent agonism and poor solubility in isoxazole series presented challenges to its further development. Based on the concept of quality by design (QbD), 5,5-disubstituted isoxazolines 3 were introduced. The chirality at 5 position of isoxazolines controlled the switch between two modes of actions, which led to a novel series of pure antagonists. This non-planar motif also conferred a change of shape of these molecules, which avoided flat structures and improved their physical properties. (C) 2014 Elsevier Ltd. All rights reserved.