butyl 4-({2-[(2R)-2-formyl-5-oxo-1-pyrrolidinyl]ethyl}thio)butanoate | 1365393-21-0

• 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: butyl 4-({2-[(2R)-2-formyl-5-oxo-1-pyrrolidinyl]ethyl}thio)butanoate
• 英文别名: butyl 4-[2-[(2R)-2-formyl-5-oxopyrrolidin-1-yl]ethylsulfanyl]butanoate
• CAS: 1365393-21-0
• 化学式: C₁₅H₂₅NO₄S
• 分子量: 315.434
• InChiKey: CBABUKIRVITBRP-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  89
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  butyl 4-({2-[(2R)-2-formyl-5-oxo-1-pyrrolidinyl]ethyl}thio)butanoate 在 盐酸 、 硼烷四氢呋喃络合物 、 四丁基氟化铵 、 水 、 sodium hydride 、 对甲苯磺酸 、 三苯基膦 、 sodium hydroxide 、 (R)-2-甲基-CBS-恶唑硼烷 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 、 mineral oil 为溶剂， 反应 9.99h， 生成 4-([2-((2R)-2-((1E,3S)-3-hydroxy-4-[3-(pyridin-3-ylmethoxy)phenyl]but-1-enyl)-5-oxopyrrolidin-1-yl)ethyl]sulfanyl)butanoic acid
  参考文献：
  名称：

  Synthesis and evaluation of γ-lactam analogs of PGE2 as EP4 and EP2/EP4 agonists

  摘要：

  To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl omega-chain moiety of the gamma-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.008
• 作为产物：
  描述：

  在 四丁基氟化铵 、 三氧化硫吡啶 、 二甲基亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 1.33h， 生成 butyl 4-({2-[(2R)-2-formyl-5-oxo-1-pyrrolidinyl]ethyl}thio)butanoate
  参考文献：
  名称：

  Discovery of Orally Available 8-Aza-5-thiaProstaglandin E1 Analogs as Highly Selective EP4 Agonists

  摘要：

  合成了 8-aza-16-aryl 前列腺素 E1 (PGE1) 和 8-aza-5-thia-16-arylPGE1 类似物，并对它们的亚型受体亲和力和 EP4 激动剂活性进行了评估，以确定具有口服疗效的亚型选择性 EP4 激动剂。通过抑制大鼠体内脂多糖（LPS）诱导的肿瘤坏死因子（TNF）-α的产生，对代表性化合物的药代动力学特征和体内疗效进行了评估。对结构-活性关系（SARs）进行了表征和展示。与之前报道的类似物 2a 相比，在测试的化合物中，有几种显示出更好的口服暴露和/或体内疗效。

  DOI：

  10.1248/cpb.59.1523

文献信息

• Synthesis and evaluation of γ-lactam analogs of PGE2 as EP4 and EP2/EP4 agonists
  作者：Tohru Kambe、Toru Maruyama、Yoshihiko Nakai、Hiroji Oida、Takayuki Maruyama、Nobutaka Abe、Akio Nishiura、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2012.04.008

  日期：2012.6

  To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl omega-chain moiety of the gamma-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented. (C) 2012 Elsevier Ltd. All rights reserved.
• Discovery of Orally Available 8-Aza-5-thiaProstaglandin E1 Analogs as Highly Selective EP4 Agonists
  作者：Tohru Kambe、Toru Maruyama、Masayuki Nakano、Yoshiyuki Yamaura、Tomoyuki Shono、Akiteru Seki、Kiyoto Sakata、Takayuki Maruyama、Hisao Nakai、Masaaki Toda

  DOI：10.1248/cpb.59.1523

  日期：——

  Analogs 8-aza-16-aryl prostaglandin E1 (PGE1) and 8-aza-5-thia-16-arylPGE1 were synthesized and evaluated with respect to their subtype receptor affinity and EP4 agonist activity for the purposes of identifying subtype-selective EP4 agonists that demonstrate oral efficacy. Using an inhibition assay of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production in rats, representative compounds were evaluated for their pharmacokinetic profiles and in vivo efficacy. Structure–activity relationships (SARs) were characterized and presented. Of the compounds tested, several demonstrated better oral exposure and/or in vivo efficacy compared with the previously reported analog 2a.

  合成了 8-aza-16-aryl 前列腺素 E1 (PGE1) 和 8-aza-5-thia-16-arylPGE1 类似物，并对它们的亚型受体亲和力和 EP4 激动剂活性进行了评估，以确定具有口服疗效的亚型选择性 EP4 激动剂。通过抑制大鼠体内脂多糖（LPS）诱导的肿瘤坏死因子（TNF）-α的产生，对代表性化合物的药代动力学特征和体内疗效进行了评估。对结构-活性关系（SARs）进行了表征和展示。与之前报道的类似物 2a 相比，在测试的化合物中，有几种显示出更好的口服暴露和/或体内疗效。