ethyl 2-({2-[(2R)-2-({tert-butyldimethylsilyloxy}methyl)-5-oxo-1-pyrrolidinyl]ethyl}thio)-1,3-thiazole-4-carboxylate | 597577-73-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 2-({2-[(2R)-2-({tert-butyldimethylsilyloxy}methyl)-5-oxo-1-pyrrolidinyl]ethyl}thio)-1,3-thiazole-4-carboxylate
• 英文别名: 2-(2-((2R)-2-(t-butyldimethylsilyloxymethyl)-5-oxopyrolidin-1-yl)ethylthio)-1,3-thiazole-4-carboxylic acid ethyl ester；2-(2-((2R)-2-(t-butyldimethylsilyloxymethyl)-5-oxopyrrolidin-1-yl)ethylthio)-1,3-thiazole-4-carboxylic acid ethyl ester；ethyl 2-[2-[(2R)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-oxopyrrolidin-1-yl]ethylsulfanyl]-1,3-thiazole-4-carboxylate
• CAS: 597577-73-6
• 化学式: C₁₉H₃₂N₂O₄S₂Si
• 分子量: 444.692
• InChiKey: DGTKFYIUOPHZIT-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.42
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  122
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-({2-[(2R)-2-({tert-butyldimethylsilyloxy}methyl)-5-oxo-1-pyrrolidinyl]ethyl}thio)-1,3-thiazole-4-carboxylate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以1.05 g的产率得到ethyl 2-({2-[(2R)-2-(hydroxymethyl)-5-oxo-1-pyrrolidinyl]ethyl}thio)-1,3-thiazole-4-carboxylate
  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：

  S-(2-{(2R)-2-[(tert-butyldimethylsilyloxy)methyl]-5-oxo-1-pyrrolidinyl}ethyl)ethanethioate 、 2-溴噻唑-4-甲酸乙酯 在 乙醇 、 potassium carbonate 作用下， 生成 ethyl 2-({2-[(2R)-2-({tert-butyldimethylsilyloxy}methyl)-5-oxo-1-pyrrolidinyl]ethyl}thio)-1,3-thiazole-4-carboxylate
  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

文献信息

• Medicinal Composition for Inhalation
  申请人：Yamamoto Shigeki

  公开号：US20080114043A1

  公开（公告）日：2008-05-15

  A medicinal composition for inhalation containing a continuous-release type prodrug of an EP2 agonist topically exhibits a prolonged bronchodilating and antiinflammatory effects. Namely, the medicinal composition for inhalation containing a continuous-release type prodrug of an EP2 agonist is useful as a safe preventive and/or a remedy for respiratory diseases (for example, asthma, pulmonary injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, adult respiratory distress syndrome, cystic fibrosis, pulmonary hypertension or the like) without causing any systemic effect such as lowering blood pressure. Thus, a safe and useful remedy for respiratory diseases is provided.

  一种含有EP2激动剂的持续释放型前药的吸入药物组合物，局部表现出持续的支气管扩张和抗炎作用。换言之，含有EP2激动剂的持续释放型前药的吸入药物组合物可作为安全的预防和/或治疗呼吸系统疾病（例如哮喘、肺损伤、肺纤维化、肺气肿、支气管炎、慢性阻塞性肺病、成人呼吸窘迫综合征、囊性纤维化、肺动脉高压等），而不会引起任何降低血压等全身作用。因此，提供了一种安全有效的呼吸系统疾病治疗药物。
• Medicinal composition for inhalation
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US07858650B2

  公开（公告）日：2010-12-28

  A medicinal composition for inhalation containing a continuous-release type prodrug of an EP2 agonist topically exhibits a prolonged bronchodilating and antiinflammatory effects. Namely, the medicinal composition for inhalation containing a continuous-release type prodrug of an EP2 agonist is useful as a safe preventive and/or a remedy for respiratory diseases (for example, asthma, pulmonary injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, adult respiratory distress syndrome, cystic fibrosis, pulmonary hypertension or the like) without causing any systemic effect such as lowering blood pressure. Thus, a safe and useful remedy for respiratory diseases is provided.

  一种用于吸入的药物组合物，其含有一种EP2激动剂的持续释放型前药，可局部表现出延长的支气管扩张和抗炎作用。换句话说，含有EP2激动剂持续释放型前药的吸入用药物组合物可作为安全的预防和/或治疗呼吸系统疾病（例如哮喘、肺部损伤、肺纤维化、肺气肿、支气管炎、慢性阻塞性肺疾病、成人呼吸窘迫综合征、囊性纤维化、肺动脉高压或类似疾病）的药物，而不会引起任何降低血压等全身性效应。因此，提供了一种安全有效的呼吸系统疾病治疗药物。
• EP1806148
  申请人：——

  公开号：——

  公开（公告）日：——