4-[(2-{(2R)-2-[(1E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)thio]butanoic acid methyl ester | 492471-49-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 4-[(2-{(2R)-2-[(1E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)thio]butanoic acid methyl ester
• 英文别名: methyl 4-[2-[(2R)-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl]ethylsulfanyl]butanoate
• CAS: 492471-49-5
• 化学式: C₁₉H₃₃NO₄S
• 分子量: 371.541
• InChiKey: WJPGQRSTIQMGJF-PMOIYJJYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[(2-{(2R)-2-[(1E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)thio]butanoic acid methyl ester 在 sodium hydroxide 氩 、 盐酸 、 水 、 乙酸乙酯 、 Brine 、 Sodium sulfate-III 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以to yield 7.5 mg of 4-[(2-{(2R)-2-[(1E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)thio]butanoic acid的产率得到4-[(2-{(2R)-2-[(1E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)thio]-butanoic acid
  参考文献：
  名称：

  2-pyrrolidone derivatives as prostanoid agonists

  摘要：

  本发明涉及8-aza前列腺素类似物，通常是EP4受体激动剂，其由式I表示：其中Q、B、X、J、Z、A和R1-R6如定义所述，其合成和用于治疗骨质疏松症和增加骨密度的用途。

  公开号：

  US06849657B2
• 作为产物：
  描述：

  (2-氧代庚基)膦酸二甲酯 在 dimethyl sulfide borane 、 potassium tert-butylate 、 四丁基氟化铵 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium chloride 、 (R)-2-甲基-CBS-恶唑硼烷 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 5.75h， 生成 4-[(2-{(2R)-2-[(1E,3S)-3-hydroxyoct-1-enyl]-5-oxopyrrolidin-1-yl}ethyl)thio]butanoic acid methyl ester
  参考文献：
  名称：

  Lactams as EP₄ Prostanoid Receptor Agonists. 3. Discovery of N-Ethylbenzoic Acid 2-Pyrrolidinones as Subtype Selective Agents

  摘要：

  Two distinct synthetic schemes were applied to access heteroatom-containing alpha-chain lactams or lactams terminated as aryl acids. The latter lactams were devised using a pharmacophore for EP4 receptor activity. gamma-Lactams were characterized for their prostanoid EP receptor affinities and EP4 activity and found to be selective for the EP2 and EP4 receptors or selective for the EP4 subtype. Benzoic acid 17 displayed enhanced in vivo exposure relative to 3.

  DOI：

  10.1021/jm049290a

文献信息

• 2-pyrrolidone derivatives as prostanoid agonists
  申请人：——

  公开号：US20030064964A1

  公开（公告）日：2003-04-03

  This invention relates to 8-aza prostanoid analogs which are generally EP 4 receptor agonists and are represented by Formula I: 1 wherein Q, B, X, J, Z, A and R 1 -R 6 are as defined, their synthesis and use for treatment of osteoporosis and increasing bone density.

  这项发明涉及一种通常为EP4受体激动剂的8-aza前列腺素类似物，其由以下式I表示：其中Q、B、X、J、Z、A和R1-R6如定义，它们的合成和用于治疗骨质疏松症和增加骨密度。
• 2 PYRROLIDONE DERIVATIVES AS PROSTANOID AGONISTS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1408961B1

  公开（公告）日：2007-07-11
• US6849657B2
  申请人：——

  公开号：US6849657B2

  公开（公告）日：2005-02-01
• Lactams as EP₄ Prostanoid Receptor Agonists. 3. Discovery of <i>N</i>-Ethylbenzoic Acid 2-Pyrrolidinones as Subtype Selective Agents
  作者：Todd R. Elworthy、Emma R. Brill、San-San Chiou、Frances Chu、Jason R. Harris、R. Than Hendricks、Jane Huang、Woongki Kim、Leang K. Lach、Tara Mirzadegan、Calvin Yee、Keith A. M. Walker

  DOI：10.1021/jm049290a

  日期：2004.12.1

  Two distinct synthetic schemes were applied to access heteroatom-containing alpha-chain lactams or lactams terminated as aryl acids. The latter lactams were devised using a pharmacophore for EP4 receptor activity. gamma-Lactams were characterized for their prostanoid EP receptor affinities and EP4 activity and found to be selective for the EP2 and EP4 receptors or selective for the EP4 subtype. Benzoic acid 17 displayed enhanced in vivo exposure relative to 3.
• 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.