methyl 5-{3-[(2R)-2-({tert-butyldimethylsilyloxy}methyl)-5-oxo-1-pyrrolidinyl]propyl}-2-thiophenecarboxylate | 431990-33-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: methyl 5-{3-[(2R)-2-({tert-butyldimethylsilyloxy}methyl)-5-oxo-1-pyrrolidinyl]propyl}-2-thiophenecarboxylate
• 英文别名: methyl 5-[3-[(2R)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate
• CAS: 431990-33-9
• 化学式: C₂₀H₃₃NO₄SSi
• 分子量: 411.638
• InChiKey: FSPSYONJMSWYIU-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.48
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  84.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 5-{3-[(2R)-2-({tert-butyldimethylsilyloxy}methyl)-5-oxo-1-pyrrolidinyl]propyl}-2-thiophenecarboxylate 在 硼烷四氢呋喃络合物 、 四丁基氟化铵 、 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 、 乙二醇二甲醚 、 乙酸乙酯 、 甲苯 、 mineral oil 为溶剂， 反应 6.25h， 生成 5-(3-{(2R)-2-[(1E,3S)-4-(3-chlorophenyl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl}propyl)thiophene-2-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：

  (R)-5-(((tert-butyldimethylsilyl)oxy)methyl)pyrrolidin-2-one 、 methyl 5-(3-bromopropyl)thiophene-2-carboxylate 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以32%的产率得到methyl 5-{3-[(2R)-2-({tert-butyldimethylsilyloxy}methyl)-5-oxo-1-pyrrolidinyl]propyl}-2-thiophenecarboxylate
  参考文献：
  名称：

  Discovery of a novel EP2/EP4 dual agonist with high subtype-selectivity

  摘要：

  A series of gamma-lactam prostaglandin E(1) analogs bearing a 16-phenyl moiety in the omega-chain and aryl moiety in the alpha-chain were synthesized and biologically evaluated. Among the tested compounds, gamma-lactam PGE analog 3 designed as a structural hybrid of 1 and 2 was discovered as the most optimized EP2/EP4 dual agonist with excellent subtype-selectivity (K(i) values: mEP2 = 9.3 nM, mEP4 = 0.41 nM). A structure-activity relationship study is presented. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.109