2-(4-{2-[2-Hydroxy-3-(4-hydroxy-phenoxy)-propylamino]-ethoxy}-phenoxy)-N-methyl-acetamide | 102528-01-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-(4-{2-[2-Hydroxy-3-(4-hydroxy-phenoxy)-propylamino]-ethoxy}-phenoxy)-N-methyl-acetamide
• 英文别名: 2-[4-[2-[[2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]ethoxy]phenoxy]-N-methylacetamide
• CAS: 102528-01-8
• 化学式: C₂₀H₂₆N₂O₆
• 分子量: 390.436
• InChiKey: AQMMWUNRLRNYTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  109
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (4-{2-[2-Hydroxy-3-(4-hydroxy-phenoxy)-propylamino]-ethoxy}-phenoxy)-acetic acid methyl ester 、 甲胺 以 乙醇 为溶剂， 生成 2-(4-{2-[2-Hydroxy-3-(4-hydroxy-phenoxy)-propylamino]-ethoxy}-phenoxy)-N-methyl-acetamide
  参考文献：
  名称：

  Selective .beta.3-adrenergic agonists of brown adipose tissue and thermogenesis. 1. [4-[2-[(2-Hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetates

  摘要：

  The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (8) has been identified as the most interesting member of a series of selective beta-3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat. In vivo it acts mainly via the related acid 10. Potency was generally markedly reduced by placing substituents on the phenyl ring of the phenoxypropanolamine unit of 8; only the 2-fluoro analogue 16 had comparable potency to 8. Other structure-activity relationships are discussed. Further testing of 8 (ICI 198157) has shown that in the rat it stimulates the beta-3-adrenergic receptor in brown adipose tissue at doses lower than those at which it affects beta-1 and beta-2 adrenergic receptors in other tissues. It increases metabolic rate, as judged by an increase in oxygen consumption, and in the genetically obese Zucker rat it causes a reduced rate of weight gain. This class of compound may be useful in the treatment of obesity in man.

  DOI：

  10.1021/jm00088a009

文献信息

• Amide derivatives
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0254532A1

  公开（公告）日：1988-01-27

  The invention concerns novel phenoxyacetic acid amide derivatives of the formula I (and pharmaceutically acceptable salts thereof) in which R1 is hydrogen or fluoro, R2 is phenyl, cyclo-alkyl, alkyl or alkenyl as defined herin, and R3 is hydrogen, methyl or ethyl, or R2 and R3 together form polymethylene as defined herein. The invention also includes pharmaceutical compositions containing the amide derivatives, means for the manufacture of the said derivatives and for their use in the treatment of obesity and related conditions and/or in the manufacture of novel medicaments.

  本发明涉及式 I 的新型苯氧乙酸酰胺衍生物（及其药学上可接受的盐），其中 R1 是氢或氟，R2 是苯基、环烷基、烷基或烯基（如本文所定义），R3 是氢、甲基或乙基，或 R2 和 R3 共同形成聚亚甲基（如本文所定义）。 本发明还包括含有酰胺衍生物的药物组合物、制造上述衍生物的方法以及用于治疗肥胖症及相关疾病和/或制造新型药物的方法。
• US4927836A
  申请人：——

  公开号：US4927836A

  公开（公告）日：1990-05-22
• US4977148A
  申请人：——

  公开号：US4977148A

  公开（公告）日：1990-12-11
• Selective .beta.3-adrenergic agonists of brown adipose tissue and thermogenesis. 1. [4-[2-[(2-Hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetates
  作者：Ralph Howe、Balbir S. Rao、Brian R. Holloway、Donald Stribling

  DOI：10.1021/jm00088a009

  日期：1992.5

  The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (8) has been identified as the most interesting member of a series of selective beta-3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat. In vivo it acts mainly via the related acid 10. Potency was generally markedly reduced by placing substituents on the phenyl ring of the phenoxypropanolamine unit of 8; only the 2-fluoro analogue 16 had comparable potency to 8. Other structure-activity relationships are discussed. Further testing of 8 (ICI 198157) has shown that in the rat it stimulates the beta-3-adrenergic receptor in brown adipose tissue at doses lower than those at which it affects beta-1 and beta-2 adrenergic receptors in other tissues. It increases metabolic rate, as judged by an increase in oxygen consumption, and in the genetically obese Zucker rat it causes a reduced rate of weight gain. This class of compound may be useful in the treatment of obesity in man.