butyl 2-[(2-{(2R)-2-[(1E,3S)-4-(3-biphenylyl)-3-hydroxy-1-buten-1-yl]-5-oxo-1-pyrrolidinyl}ethyl)thio]-1,3-thiazole-4-carboxylate | 1365177-97-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: butyl 2-[(2-{(2R)-2-[(1E,3S)-4-(3-biphenylyl)-3-hydroxy-1-buten-1-yl]-5-oxo-1-pyrrolidinyl}ethyl)thio]-1,3-thiazole-4-carboxylate
• CAS: 1365177-97-4
• 化学式: C₃₀H₃₄N₂O₄S₂
• 分子量: 550.743
• InChiKey: JAEBLEOMIFRAOZ-GZCDYTBJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.01
• 重原子数：
  38.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  79.73
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  butyl 2-[(2-{(2R)-2-[(1E,3S)-4-(3-biphenylyl)-3-hydroxy-1-buten-1-yl]-5-oxo-1-pyrrolidinyl}ethyl)thio]-1,3-thiazole-4-carboxylate 在 sodium hydroxide 、 盐酸 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 2.0h， 以78%的产率得到2-[(2-{(2R)-2-[(1E,3S)-4-(1,1'-biphenyl-3-yl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)sulfanyl]-1,3-thiazole-4-carboxylic acid
  参考文献：
  名称：

  Discovery of novel prostaglandin analogs as potent and selective EP2/EP4 dual agonists

  摘要：

  To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of c-lactam prostaglandin E analogs bearing a 16-phenyl x-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.018
• 作为产物：
  描述：

  在 硼烷四氢呋喃络合物 、 (R)-2-甲基-CBS-恶唑硼烷 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 0.42h， 以67 mg的产率得到butyl 2-[(2-{(2R)-2-[(1E,3S)-4-(3-biphenylyl)-3-hydroxy-1-buten-1-yl]-5-oxo-1-pyrrolidinyl}ethyl)thio]-1,3-thiazole-4-carboxylate
  参考文献：
  名称：

  Discovery of novel prostaglandin analogs as potent and selective EP2/EP4 dual agonists

  摘要：

  To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of c-lactam prostaglandin E analogs bearing a 16-phenyl x-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.018