(Z)-7-{(1R,2R,3R,5R)-5-Chloro-2-[(E)-(S)-4-(1-ethyl-cyclobutyl)-4-hydroxy-but-1-enyl]-3-hydroxy-cyclopentyl}-hept-5-enoic acid methyl ester | 433231-76-6

• 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: (Z)-7-{(1R,2R,3R,5R)-5-Chloro-2-[(E)-(S)-4-(1-ethyl-cyclobutyl)-4-hydroxy-but-1-enyl]-3-hydroxy-cyclopentyl}-hept-5-enoic acid methyl ester
• CAS: 433231-76-6
• 化学式: C₂₃H₃₇ClO₄
• 分子量: 412.997
• InChiKey: OAEHECZSLJRHCS-SDQZANPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.77
• 重原子数：
  28.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  66.76
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (Z)-7-{(1R,2R,3R,5R)-5-Chloro-2-[(E)-(S)-4-(1-ethyl-cyclobutyl)-4-hydroxy-but-1-enyl]-3-hydroxy-cyclopentyl}-hept-5-enoic acid methyl ester 在 palladium on activated charcoal sodium hydroxide 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 生成 7-{(1R,2R,3R,5R)-5-Chloro-2-[(S)-4-(1-ethyl-cyclobutyl)-4-hydroxy-butyl]-3-hydroxy-cyclopentyl}-heptanoic acid
  参考文献：
  名称：

  A Practical Synthesis and Biological Evaluation of 9-Halogenated PGF Analogues

  摘要：

  A series of 9-halo PGF analogues 1-2 and 5-13 were synthesized and biologically evaluated. Among the compounds, 2 was the best EP2-receptor agonist. A practical method of synthesizing 2 via the Julia olefination of an aldehyde 3 with an optically active sulfone 4, which was prepared by Sharpless asymmetric epoxidation of 15, was developed. Other 9-halogenated PGF analogues were synthesized essentially by the same procedure and evaluated. The absolute configuration of 16-OH of 2 was determined as S by the X-ray analysis of a salt consisting of a 1/1 molar ratio of 2 and L-lysine. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00008-1
• 作为产物：
  描述：

  (3R)-4,4-(trimethylene)hexane-1,3-diol 在 Oxone 、 sodium hydroxide 、 正丁基锂 、 三甲基氯硅烷 、 四丁基溴化铵 、 对甲苯磺酸 、 magnesium 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 4.0h， 生成 (Z)-7-{(1R,2R,3R,5R)-5-Chloro-2-[(E)-(S)-4-(1-ethyl-cyclobutyl)-4-hydroxy-but-1-enyl]-3-hydroxy-cyclopentyl}-hept-5-enoic acid methyl ester
  参考文献：
  名称：

  高选择性 EP2 受体激动剂的合成

  摘要：

  开发了一种合成前列腺素 EP2 受体激动剂 1 的实用方法。该方法包括使用 Sharpless 不对称环氧化程序从烯丙醇 4 制备醛 2 与旋光砜 3 的镁介导的 Julia 烯化。

  DOI：

  10.1055/s-2002-19781

文献信息

• Development of a highly selective EP2-receptor agonist. Part 2: identification of 16-Hydroxy-17,17-trimethylene 9β-chloro PGF derivatives
  作者：Kousuke Tani、Atsushi Naganawa、Akiharu Ishida、Hiromu Egashira、Kenji Sagawa、Hiroyuki Harada、Mikio Ogawa、Takayuki Maruyama、Shuichi Ohuchida、Hisao Nakai、Kigen Kondo、Masaaki Toda

  DOI：10.1016/s0968-0896(01)00370-4

  日期：2002.4

  Further chemical modification of 1a and 2 was undertaken to identify a more chemically stable selective EP2-receptor agonist for development as a clinical candidate. 9beta-Chloro PG analogues 4a-e and 5a, c-e were found to be potent and selective EP2-receptor agonists. Among them, the compound 4aLy, which is a chemically stabilized lysine salt of 4a, exhibited an excellent profile both in biological activities and physicochemical properties. The agonist 4aLy was found to suppress uterine motility in anesthetized pregnant rats, while PGE(2) stimulated uterine motility. Structure-activity relationships (SARs) are discussed. (C) 2002 Elsevier Science Ltd. All rights reserved.