ethyl (4R,5E,7S)-4-amino-8-(3-chlorophenyl)-7-hydroxy-5-octenoate trifluoroacetate | 1365177-44-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl (4R,5E,7S)-4-amino-8-(3-chlorophenyl)-7-hydroxy-5-octenoate trifluoroacetate
• CAS: 1365177-44-1
• 化学式: C₂HF₃O₂*C₁₆H₂₂ClNO₃
• 分子量: 425.833
• InChiKey: WTGZHXQCTULVSC-OMOOGMCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  28.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  109.85
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl [3-(2-bromoethyl)phenyl]acetate 、 ethyl (4R,5E,7S)-4-amino-8-(3-chlorophenyl)-7-hydroxy-5-octenoate trifluoroacetate 在 碳酸氢钠 、 sodium hydroxide 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 [3-(2-{(2R)-2-[(1E,3S)-4-(3-chlorophenyl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)phenyl]acetic 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：

  (R)-ethyl 4-(tert-butoxycarbonylamino)-5-oxopentanoate 在 硼烷四氢呋喃络合物 、 sodium hydride 、 (R)-2-甲基-CBS-恶唑硼烷 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 、 mineral oil 为溶剂， 反应 5.08h， 生成 ethyl (4R,5E,7S)-4-amino-8-(3-chlorophenyl)-7-hydroxy-5-octenoate trifluoroacetate
  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