N-[4-({(2R,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)phenyl]-4-{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}benzenesulfonamide | 1190390-47-6

• 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: N-[4-({(2R,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)phenyl]-4-{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}benzenesulfonamide
• 英文别名: trans-N-(4-(((2S,5R)-5-((R)-hydroxy(phenyl)methyl)pyrrolidin-2-yl)methyl)phenyl)-4-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)benzenesulfonamide；N-[4-[[(2R,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl]methyl]phenyl]-4-[4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]benzenesulfonamide
• CAS: 1190390-47-6
• 化学式: C₃₄H₃₀F₃N₃O₃S₂
• 分子量: 649.758
• InChiKey: CVNUDPVQPWCUGZ-BHYWQNONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 盐酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 N-[4-({(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)phenyl]-4-{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}benzenesulfonamide 、 N-[4-({(2R,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)phenyl]-4-{4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}benzenesulfonamide
  参考文献：
  名称：

  Design of a novel pyrrolidine scaffold utilized in the discovery of potent and selective human β3 adrenergic receptor agonists

  摘要：

  A novel class of human beta(3)-adrenergic receptor agonists was designed in effort to improve selectivity and metabolic stability versus previous disclosed beta(3)-AR agonists. As observed, many of the beta(3)-AR agonists seem to need the acyclic ethanolamine core for agonist activity. We have synthesized derivatives that constrained this moiety by introduction of a pyrrolidine. This unique modification maintains human beta(3) functional potency with improved selectivity versus ancillary targets and also eliminates the possibility of the same oxidative metabolites formed from cleavage of the N-C bond of the ethanolamine. Compound 39 exhibited excellent functional beta(3) agonist potency across species with good pharmacokinetic properties in rat, dog, and rhesus monkeys. Early de-risking of this novel pyrrolidine core (44) via full AMES study supports further research into various new beta(3)-AR agonists containing the pyrrolidine moiety. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.087

文献信息

• 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。
• [EN] HYDROXYMETHYL PYRROLIDINES AS BETA 3 ADRENERGIC RECEPTOR AGONISTS<br/>[FR] HYDROXYMÉTHYL PYRROLIDINES EN TANT QU'AGONISTES DE RÉCEPTEUR BÊTA 3 ADRÉNERGIQUE
  申请人：MERCK & CO INC

  公开号：WO2009124167A1

  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.

  本发明提供了化合物(I)、其制药组合物以及使用它们治疗或预防由β3肾上腺素能受体激活介导的疾病的方法。
• Hydroxymethyl pyrrolidines as β3 adrenergic receptor agonists
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08247415B2

  公开（公告）日：2012-08-21

  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、其制药组合物以及使用该化合物治疗或预防由β3-肾上腺素受体激活介导的疾病的方法。
• Hydroxymethyl pyrrolidines as beta 3 adrenergic receptor agonists
  申请人：Berger Richard

  公开号：US08399480B2

  公开（公告）日：2013-03-19

  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.

  本发明提供了公式（I）的化合物，其药物组成物以及使用该药物组成物治疗或预防由β3-肾上腺素受体激活介导的疾病的方法。
• US8247415B2
  申请人：——

  公开号：US8247415B2

  公开（公告）日：2012-08-21