tert-butyl (2S,5R)-2-(4-((R)-2-ethyl-5,6-dihydro-4H-cyclopenta[d]thiazole-4-carboxamido)benzyl)-5-((R)-hydroxy(pyridin-3-yl)methyl)pyrrolidine-1-carboxylate | 1558058-05-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (2S,5R)-2-(4-((R)-2-ethyl-5,6-dihydro-4H-cyclopenta[d]thiazole-4-carboxamido)benzyl)-5-((R)-hydroxy(pyridin-3-yl)methyl)pyrrolidine-1-carboxylate
• CAS: 1558058-05-1
• 化学式: C₃₁H₃₈N₄O₄S
• 分子量: 562.733
• InChiKey: SKSHSECMCCTDLM-GOIZPCHYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.81
• 重原子数：
  40.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  104.65
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,5R)-2-(4-((R)-2-ethyl-5,6-dihydro-4H-cyclopenta[d]thiazole-4-carboxamido)benzyl)-5-((R)-hydroxy(pyridin-3-yl)methyl)pyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (R)-2-ethyl-N-(4-(((2S,5R)-5-((R)-hydroxy(pyridin-3-yl)methyl)pyrrolidin-2-yl)methyl)phenyl)-5,6-dihydro-4H-cyclopenta[d]thiazole-4-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Conformationally Restricted Acetanilides as Potent and Selective β₃Adrenergic Receptor Agonists for the Treatment of Overactive Bladder

  摘要：

  A series of conformationally restricted acetanilides were synthesized and evaluated as beta(3)-adrenergic receptor agonists (beta(3)-AR) for the treatment of overactive bladder (OAB). Optimization studies identified a five-membered ring as the preferred conformational lock of the acetanilide. Further optimization of both the aromatic and thiazole regions led to compounds such as 19 and 29, which have a good balance of potency and selectivity. These compounds have significantly reduced intrinsic clearance compared to our initial series of pyridylethanolamine beta(3)-AR agonists and thus have improved unbound drug exposures. Both analogues demonstrated dose dependent beta(3)-AR mediated responses in a rat bladder hyperactivity model.

  DOI：

  10.1021/jm4017224
• 作为产物：
  描述：

  4-methoxybenzyl ((1R,2R)-1-((tert-butyldimethylsilyl)oxy)-1-(6-chloropyridin-3-yl)hex-5-yn-2-yl)carbamate 在 四氢吡咯 、 copper(l) iodide 、 palladium 10% on activated carbon 、 C₃₄H₂₉Cl₂FeP₂Pd⁽¹⁺⁾ 、 四丁基氟化铵 、 氢气 、 potassium acetate 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、344.75 kPa 条件下， 反应 36.5h， 生成 tert-butyl (2S,5R)-2-(4-((R)-2-ethyl-5,6-dihydro-4H-cyclopenta[d]thiazole-4-carboxamido)benzyl)-5-((R)-hydroxy(pyridin-3-yl)methyl)pyrrolidine-1-carboxylate 、
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Conformationally Restricted Acetanilides as Potent and Selective β₃Adrenergic Receptor Agonists for the Treatment of Overactive Bladder

  摘要：

  A series of conformationally restricted acetanilides were synthesized and evaluated as beta(3)-adrenergic receptor agonists (beta(3)-AR) for the treatment of overactive bladder (OAB). Optimization studies identified a five-membered ring as the preferred conformational lock of the acetanilide. Further optimization of both the aromatic and thiazole regions led to compounds such as 19 and 29, which have a good balance of potency and selectivity. These compounds have significantly reduced intrinsic clearance compared to our initial series of pyridylethanolamine beta(3)-AR agonists and thus have improved unbound drug exposures. Both analogues demonstrated dose dependent beta(3)-AR mediated responses in a rat bladder hyperactivity model.

  DOI：

  10.1021/jm4017224