3-(3-{(2R)-2-[(1E,3S)-4-(3-chlorophenyl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl}phenyl)propanoic acid | 1365176-80-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 3-(3-{(2R)-2-[(1E,3S)-4-(3-chlorophenyl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl}phenyl)propanoic acid
• 英文别名: 3-[3-[(2R)-2-[(E,3S)-4-(3-chlorophenyl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl]phenyl]propanoic acid
• CAS: 1365176-80-2
• 化学式: C₂₃H₂₄ClNO₄
• 分子量: 413.901
• InChiKey: XUWVCPYSUSCWLU-YVRUHCSNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-(-)-5-羟甲基-2-吡咯烷酮 在 盐酸 、 1,1'-双(二苯基膦)二茂铁 、 sodium tetrahydroborate 、 硼烷四氢呋喃络合物 、 nickel(II) chloride hexahydrate 、 三氟甲磺酸 、 potassium tert-butylate 、 palladium diacetate 、 三氧化硫吡啶 、 sodium hydride 、 二甲基亚砜 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 (R)-2-甲基-CBS-恶唑硼烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 5,5-dimethyl-1,3-cyclohexadiene 、 二氯甲烷 、 乙酸乙酯 、 甲苯 、 mineral oil 为溶剂， 反应 23.25h， 生成 3-(3-{(2R)-2-[(1E,3S)-4-(3-chlorophenyl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl}phenyl)propanoic 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

文献信息

• Discovery of novel prostaglandin analogs as potent and selective EP2/EP4 dual agonists
  作者：Tohru Kambe、Toru Maruyama、Yoshihiko Nakai、Hideyuki Yoshida、Hiroji Oida、Takayuki Maruyama、Nobutaka Abe、Akio Nishiura、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2012.02.018

  日期：2012.4

  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.