(R)-N-[2-(4-aminophenyl)ethyl]-2-hydroxy-2-(3-pyridyl)ethylcarbamic acid 1,1-dimethylethyl ester | 173901-05-8

• 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: (R)-N-[2-(4-aminophenyl)ethyl]-2-hydroxy-2-(3-pyridyl)ethylcarbamic acid 1,1-dimethylethyl ester
• 英文别名: tert-butyl N-[2-(4-aminophenyl)ethyl]-N-[(2R)-2-hydroxy-2-pyridin-3-ylethyl]carbamate
• CAS: 173901-05-8
• 化学式: C₂₀H₂₇N₃O₃
• 分子量: 357.453
• InChiKey: GSSXTGKHFUJCPL-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  88.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-N-[2-(4-aminophenyl)ethyl]-2-hydroxy-2-(3-pyridyl)ethylcarbamic acid 1,1-dimethylethyl ester 在 吡啶 、 硫化氢 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 (R)-N-[4-[2-[N-(1,1-dimethylethoxycarbonyl)-N-[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(aminothiocarbonyl)benzenesulfonamide
  参考文献：
  名称：

  发现有效的，口服生物利用的β（3）肾上腺素能受体激动剂，（R）-N- [4- [2-[[[2-羟基-2-（3-吡啶基）乙基]氨基]乙基]苯基] -4 -[4- [4-（三氟甲基）苯基]噻唑-2-基]苯磺酰胺。

  摘要：

  作为我们对口服生物利用的β（3）肾上腺素能受体激动剂的研究的一部分，我们鉴定了一系列具有取代的噻唑苯磺酰胺药效基团的吡啶基乙醇胺类似物，它们是有效的人β（3）激动剂，对其他人β受体具有优异的选择性亚型。这些化合物中的几种在犬中也表现出改善的药代动力学特征。例如，噻唑磺酰胺2e（R = 4-F（3）CC（6）H（4））是有效的全β（3）激动剂（EC（50）= 3.6 nM，94％活化），其> 600-选择性比人类的beta（1）和beta（2）受体高，这在几种哺乳动物中也表现出良好的口服生物利用度，并且作用时间延长。

  DOI：

  10.1021/jm000286i
• 作为产物：
  描述：

  2-(4-氨基苯)乙胺 以 四氢呋喃 、 甲醇 为溶剂， 生成 (R)-N-[2-(4-aminophenyl)ethyl]-2-hydroxy-2-(3-pyridyl)ethylcarbamic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Malamas; Largis; Gunawan, Medicinal Chemistry Research, 2000, vol. 10, # 3, p. 164 - 177

  摘要：

  DOI：

文献信息

• Discovery of a Potent, Orally Bioavailable β₃ Adrenergic Receptor Agonist, (<i>R</i>)-<i>N</i>-[4-[2-[[2-Hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[4-[4-(trifluoromethyl)phenyl]thiazol-2-yl]benzenesulfonamide
  作者：Robert J. Mathvink、J. Samuel Tolman、Dawn Chitty、Mari R. Candelore、Margaret A. Cascieri、Lawrence F. Colwell、Liping Deng、William P. Feeney、Michael J. Forrest、Gary J. Hom、D. Euan MacIntyre、Randall R. Miller、Ralph A. Stearns、Laurie Tota、Matthew J. Wyvratt、Michael H. Fisher、Ann E. Weber

  DOI：10.1021/jm000286i

  日期：2000.10.1

  possessing a substituted thiazole benzenesulfonamide pharmacophore that are potent human beta(3) agonists with excellent selectivity against other human beta receptor subtypes. Several of these compounds also exhibited an improved pharmacokinetic profile in dogs. For example, thiazole sulfonamide 2e (R = 4-F(3)C-C(6)H(4)) is a potent full beta(3) agonist (EC(50) = 3.6 nM, 94% activation) with >600-fold selectivity

  作为我们对口服生物利用的β（3）肾上腺素能受体激动剂的研究的一部分，我们鉴定了一系列具有取代的噻唑苯磺酰胺药效基团的吡啶基乙醇胺类似物，它们是有效的人β（3）激动剂，对其他人β受体具有优异的选择性亚型。这些化合物中的几种在犬中也表现出改善的药代动力学特征。例如，噻唑磺酰胺2e（R = 4-F（3）CC（6）H（4））是有效的全β（3）激动剂（EC（50）= 3.6 nM，94％活化），其> 600-选择性比人类的beta（1）和beta（2）受体高，这在几种哺乳动物中也表现出良好的口服生物利用度，并且作用时间延长。
• Substituted sulfonamides as selective .beta..sub.3 agonists for the
  申请人：Merck & Co., Inc.

  公开号：US05561142A1

  公开（公告）日：1996-10-01

  Substituted sulfonamides are selective .beta..sub.3 adrenergic receptor agonists with very little .beta..sub.1 and .beta..sub.2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in cells. The compounds thus have potent activity in the treatment of Type II diabetes and obesity. The compounds can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduced neurogenic inflammation or as antidepressant agents. The compounds are prepared by coupling an aminoalkylphenyl-sulfonamide with an appropriately substituted epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for increasing gut motility are also disclosed.

  取代磺酰胺是具有极少量β1和β2肾上腺素受体活性的选择性β3肾上腺素受体激动剂，因此这些化合物能够增加细胞的脂解和能量消耗。因此，这些化合物在治疗II型糖尿病和肥胖症方面具有强效活性。这些化合物也可用于降低甘油三酯水平和胆固醇水平，或提高高密度脂蛋白水平，或减少肠道运动性。此外，这些化合物也可用于减少神经源性炎症或作为抗抑郁剂。这些化合物是通过将氨基烷基苯磺酰胺与适当取代的环氧化物偶联制备而成。该发明还揭示了在治疗糖尿病和肥胖症以及降低甘油三酯水平和胆固醇水平或提高高密度脂蛋白水平或增加肠道运动性方面使用这些化合物的组合物和方法。
• Thiazole benzenesulfonamides as .beta.3 agonists for treatment of
  申请人：Merck & Co., Inc.

  公开号：US06011048A1

  公开（公告）日：2000-01-04

  Thiazole substituted benzenesulfonamides are .beta..sub.3 adrenergic receptor agonists with very little .beta..sub.1 and .beta..sub.2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in cells. The compounds thus have potent activity in the treatment of Type II diabetes and obesity. The compounds can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduced neurogenic inflammation or as antidepressant agents. The compounds are prepared by coupling an aminoalkylphenyl-sulfonamide with an appropriately substituted epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for decreasing gut motility are also disclosed.

  噻唑取代的苯磺酰胺是β3肾上腺素受体激动剂，其β1和β2肾上腺素受体活性极低，因此这些化合物能够增加细胞内的脂解和能量消耗。因此，这些化合物在治疗II型糖尿病和肥胖症方面具有强效活性。这些化合物还可以用于降低甘油三酯水平和胆固醇水平，或提高高密度脂蛋白水平，或减少肠道蠕动。此外，这些化合物还可以用于减少神经源性炎症或作为抗抑郁剂。这些化合物是通过将氨基烷基苯磺酰胺与适当取代的环氧化物偶联制备而成。本文还公开了在治疗糖尿病和肥胖症以及降低甘油三酯水平和胆固醇水平或提高高密度脂蛋白水平或减少肠道蠕动方面使用这些化合物的组合物和方法。
• Potent, selective human β3 adrenergic receptor agonists containing a substituted indoline-5-sulfonamide pharmacophore
  作者：Robert J Mathvink、Anna Maria Barritta、Mari R Candelore、Margaret A Cascieri、Liping Deng、Laurie Tota、Catherine D Strader、Matthew J Wyvratt、Michael H Fisher、Ann E Weber

  DOI：10.1016/s0960-894x(99)00277-2

  日期：1999.7

  A series of compounds possessing an N-substituted indoline-5-sulfonamide pharmacophore was prepared and evaluated for their human beta(3) adrenergic receptor agonist activity. The SAR of a wide range of urea and heterocyclic substituents is discussed. 4-Octyl thiazole compound 8c was the most potent and selective compound in the series, with 2800-fold selectivity over beta(1) binding and 1400-fold selectivity over beta(2) binding (C) 1999 Elsevier Science Ltd. All rights reserved.
• Human β3 adrenergic receptor agonists containing cyclic ureidobenzenesulfonamides
  作者：Emma R. Parmee、Elizabeth M. Naylor、Leroy Perkins、Vincent J. Colandrea、Hyun O. Ok、Mari R. Candelore、Margaret A. Cascieri、Liping Deng、William P. Feeney、Michael J. Forrest、Gary J. Hom、D.Euan MacIntyre、Randall R. Miller、Ralph A. Stearns、Catherine D. Strader、Laurie Tota、Matthew J. Wyvratt、Michael H. Fisher、Ann E. Weber

  DOI：10.1016/s0960-894x(99)00073-6

  日期：1999.3

  Human beta(3) adrenergic receptor agonists containing 5-membered ring ureas were shown to be potent partial agonists with excellent selectivity over beta(1) and beta(2) binding. L-760,087 (4a) and L-764,646 (5a) (beta(3) EC50 = 18 and 14 nM, respectively) stimulate lipolysis in rhesus monkeys (ED50 = 0.2 and 0.1 mg/kg, respectively) with minimal effects on heart rate. Oral absorption in dogs is improved over other urea analogs. (C) 1999 Elsevier Science Ltd. All rights reserved.