5-[7-[(5R)-5-(1,3-benzothiazol-2-yl)-5-methyl-4H-1,2-oxazol-3-yl]-3-(4-fluorophenyl)-4-oxoquinazolin-2-yl]pentanoic acid | 1373276-16-4

• 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-[7-[(5R)-5-(1,3-benzothiazol-2-yl)-5-methyl-4H-1,2-oxazol-3-yl]-3-(4-fluorophenyl)-4-oxoquinazolin-2-yl]pentanoic acid
• CAS: 1373276-16-4
• 化学式: C₃₀H₂₅FN₄O₄S
• 分子量: 556.617
• InChiKey: QKEDYULXVMFFDO-SSEXGKCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  133
• 氢给体数：
  1
• 氢受体数：
  9

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-[7-[(5R)-5-(1,3-benzothiazol-2-yl)-5-methyl-4H-1,2-oxazol-3-yl]-3-(4-fluorophenyl)-4-oxoquinazolin-2-yl]pentanoic acid 、 5-[7-[(5S)-5-(1,3-benzothiazol-2-yl)-5-methyl-4H-1,2-oxazol-3-yl]-3-(4-fluorophenyl)-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

• QUINAZOLINONE-TYPE COMPOUNDS AS CRTH2 ANTAGONISTS
  申请人：Aslanian Robert G.

  公开号：US20130210805A1

  公开（公告）日：2013-08-15

  This application provides for compounds of the formula Formula I or a pharmaceutically acceptable salt thereof, wherein the individual variables are defined herein, as well as processes to prepare these compounds, pharmaceutical compositions comprising the same and their use in treating disease state associated with the CRTH 2 receptor.

  该应用程序提供了公式I或其药学上可接受的盐的化合物，其中各个变量在此定义，以及制备这些化合物的过程，包括这些化合物的制药组合物以及它们在治疗与CRTH2受体相关的疾病状态中的使用。
• US8927559B2
  申请人：——

  公开号：US8927559B2

  公开（公告）日：2015-01-06
• 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.