2-(叔丁氧基羰基)-4,5,6,7-四氢苯并[d]噻唑-4-羧酸 | 1190391-84-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-(叔丁氧基羰基)-4,5,6,7-四氢苯并[d]噻唑-4-羧酸
• 英文名称: 2-((tert-butoxycarbonyl)amino)-4,5,6,7-tetrahydrobenzo[d]thiazole-4-carboxylic acid
• 英文别名: 2-[(tert-butoxycarbonyl)amino]-4,5,6,7-tetrahydro-1,3-benzothiazole-4-carboxylic acid；2-[(2-methylpropan-2-yl)oxycarbonylamino]-4,5,6,7-tetrahydro-1,3-benzothiazole-4-carboxylic acid
• CAS: 1190391-84-4
• 化学式: C₁₃H₁₈N₂O₄S
• 分子量: 298.363
• InChiKey: QQAPPTIFMLODJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2934200090

反应信息

• 作为反应物：
  描述：

  2-(叔丁氧基羰基)-4,5,6,7-四氢苯并[d]噻唑-4-羧酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (S)-2-amino-N-(4-(((2S,5R)-5-((R)-hydroxy(phenyl)methyl)pyrrolidin-2-yl)methyl)phenyl)-4,5,6,7-tetrahydrobenzo[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：

  3-溴-2-氧-环己酮甲酸乙酯 在 4-二甲氨基吡啶 、 水 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 生成 2-(叔丁氧基羰基)-4,5,6,7-四氢苯并[d]噻唑-4-羧酸
  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

文献信息

• [EN] COMBINATION THERAPY USING A BETA 3 ADRENERGIC RECEPTOR AGONIST AND AN ANTIMUSCARINIC AGENT<br/>[FR] POLYTHÉRAPIE UTILISANT UN AGONISTE DES RÉCEPTEURS ADRÉNERGIQUES BÊTA-3 ET UN AGENT ANTIMUSCARINIQUE
  申请人：MERCK SHARP & DOHME

  公开号：WO2011043942A1

  公开（公告）日：2011-04-14

  Described herein is an improved method of treating overactive bladder, wherein the method comprises administering to a patient in need thereof a beta 3 adrenergic receptor agonist, an antimuscarinic agent, and an optional selective M2 antagonist. Such combination therapy provides improved efficacy and/or reduced side effects.

  本文描述了一种改进的治疗过度活跃膀胱的方法，其中该方法包括向需要的患者施用β3肾上腺能受体激动剂、抗胆碱药物和可选的选择性M2拮抗剂。这种联合疗法提供了改善的疗效和/或减少的副作用。
• HYDROXYMETHYL PYRROLIDINES AS BETA 3 ADRENERGIC RECEPTOR AGONISTS
  申请人：Berger Richard

  公开号：US20090253705A1

  公开（公告）日：2009-10-08

  The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of β3-adrenoceptor.

  本发明提供了式(I)的化合物，其药物组成物以及使用该化合物在治疗或预防由β3-肾上腺素受体激活介导的疾病的方法。
• COMBINATION THERAPY USING A BETA 3 ADRENERGIC RECEPTOR AGONISTS AND AN ANTIMUSCARINIC AGENT
  申请人：Edmondson Scott D.

  公开号：US20120202819A1

  公开（公告）日：2012-08-09

  Described herein is an improved method of treating overactive bladder, wherein the method comprises administering to a patient in need thereof a beta 3 adrenergic receptor agonist, an antimuscarinic agent, and an optional selective M 2 antagonist. Such combination therapy provides improved efficacy and/or reduced side effects.

  本文描述了一种改进的治疗过度活跃膀胱的方法，其中该方法包括向需要治疗的患者施用β3肾上腺素能受体激动剂、抗胆碱药物和可选的选择性M2拮抗剂。这种联合治疗提供了更好的疗效和/或减少了副作用。
• US8247415B2
  申请人：——

  公开号：US8247415B2

  公开（公告）日：2012-08-21
• US8399480B2
  申请人：——

  公开号：US8399480B2

  公开（公告）日：2013-03-19