methyl N-benzyl-<4-<2-<(2-hydroxy-3-phenoxypropyl)amino>ethoxy>phenoxy>acetate | 107332-61-6

• 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: methyl N-benzyl-<4-<2-<(2-hydroxy-3-phenoxypropyl)amino>ethoxy>phenoxy>acetate
• 英文别名: methyl 2-p-(2-[N-benzyl-(2-hydroxy-3-phenoxypropyl)-amino]ethoxy)phenoxyacetate；methyl 2-p-(2-[N-benzyl-(2-hydroxy-3-phenoxypropyl)amino]ethoxy)phenoxyacetate；Methyl 2-[4-[2-[benzyl-(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate
• CAS: 107332-61-6
• 化学式: C₂₇H₃₁NO₆
• 分子量: 465.546
• InChiKey: PLBHREIOTIHTIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl N-benzyl-<4-<2-<(2-hydroxy-3-phenoxypropyl)amino>ethoxy>phenoxy>acetate 在 palladium on activated charcoal 甲酸 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 60.0~100.0 ℃ 、2.0 MPa 条件下， 反应 51.0h， 生成 methyl N-methyl-<4-<2-<(2-hydroxy-3-phenoxypropyl)amino>ethoxy>phenoxy>acetate
  参考文献：
  名称：

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

  摘要：

  The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (1) (R1 = OMe) had previously 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 1 (R1 = OH). Amides have been examined to determine whether they have advantages over the ester. In particular, in the rat and dog the half-lives of amides of appropriate potency were no longer than those of the ester. The amide (S)-4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]-N-(2-methoxyethyl)phenoxyacetamide [S-27, ICI D7114] was selected as having properties consistent with a sustained-release formulation should that prove necessary. Unlike the ester it is resistant to hydrolysis in the gut lumen. Further testing of ICI D7114 has shown that in the rat, cat, and dog 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. Slimming effects were observed in the dog. ICI D7114 may be a selective thermogenic agent in man and may be useful in the treatment of obesity and diabetes.

  DOI：

  10.1021/jm00088a010
• 作为产物：
  描述：

  N-benzyl-2-(4-hydroxyphenoxy)ethylamine hydrochloride 在 potassium carbonate 、 potassium iodide 作用下， 以 异丙醇 、 丙酮 为溶剂， 反应 96.0h， 生成 methyl N-benzyl-<4-<2-<(2-hydroxy-3-phenoxypropyl)amino>ethoxy>phenoxy>acetate
  参考文献：
  名称：

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

  摘要：

  The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (1) (R1 = OMe) had previously 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 1 (R1 = OH). Amides have been examined to determine whether they have advantages over the ester. In particular, in the rat and dog the half-lives of amides of appropriate potency were no longer than those of the ester. The amide (S)-4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]-N-(2-methoxyethyl)phenoxyacetamide [S-27, ICI D7114] was selected as having properties consistent with a sustained-release formulation should that prove necessary. Unlike the ester it is resistant to hydrolysis in the gut lumen. Further testing of ICI D7114 has shown that in the rat, cat, and dog 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. Slimming effects were observed in the dog. ICI D7114 may be a selective thermogenic agent in man and may be useful in the treatment of obesity and diabetes.

  DOI：

  10.1021/jm00088a010

文献信息

• Amide derivatives
  申请人：Imperial Chemical Industries PLC

  公开号：US04927836A1

  公开（公告）日：1990-05-22

  The invention concerns novel phenoxyacetic acid amide derivatives of the formula I (and pharmaceutically acceptable salts thereof) in which R.sup.1 is hydrogen or fluoro, R.sup.2 is phenyl, cycloalkyl, alkyl or alkenyl as defined herein, and R.sup.3 is hydrogen, methyl or ethyl, or R.sup.2 and R.sup.3 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.

  该发明涉及公式I的新颖苯氧乙酸酰胺衍生物（及其药用可接受的盐），其中R.sup.1为氢或氟，R.sup.2为苯基，环烷基，烷基或烯基，如本文所定义，R.sup.3为氢，甲基或乙基，或R.sup.2和R.sup.3共同形成聚亚甲基，如本文所定义。该发明还包括含有酰胺衍生物的药物组合物，用于制造所述衍生物的手段，以及用于治疗肥胖和相关疾病和/或制造新型药物的用途。
• Phenyl ethers
  申请人：Imperial Chemical Industries PlC

  公开号：US04772631A1

  公开（公告）日：1988-09-20

  The invention concerns a series of novel phenoxyacetic acid ethers (and pharmaceutically acceptable salts thereof) of the formula I in which R.sup.1 is H or F, R.sup.2 and R.sup.3 are H or (1-3C)alkyl, Z is CH.sub.2 OH or a group --CO.R.sup.4 in which R.sup.4 is OH, NH.sub.2 or (1-6C)alkoxy. The invention also includes pharmaceutical compositions for use in treating obesity and related conditions and provides processes for the manufacture of the novel ethers.

  本发明涉及一系列新型苯氧基乙酸醚（及其药学上可接受的盐），其化学式为I式，其中R.sup.1为H或F，R.sup.2和R.sup.3为H或（1-3C）烷基，Z为CH.sub.2 OH或一个--CO.R.sup.4基团，其中R.sup.4为OH，NH.sub.2或（1-6C）烷氧基。本发明还包括用于治疗肥胖和相关疾病的制药组合物，并提供了制造新型醚的方法。
• 2-Hydroxy-3-phenoxypropyl amines
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0210849A1

  公开（公告）日：1987-02-04

  The invention concerns a series of phenoxyacetic acid ethers (and pharmaceutically acceptable salts thereof) of the formula I in which R1 is H or F, R2 and R3 are H or alkyl, Z is CH2OH or a group -CO.R4 in which R4 is OH, NH2 or alkoxy. The invention also includes pharmaceutical compositions for use in treating obesity and related conditions and provides processes for the manufacture of the ethers.

  本发明涉及一系列式 I 的苯氧乙酸醚（及其药学上可接受的盐）。 其中 R1 是 H 或 F、 R2和R3为H或烷基，Z为CH2OH或基团-CO.R4，其中R4为OH、NH2或烷氧基。本发明还包括用于治疗肥胖症及相关疾病的药物组合物，并提供了醚类化合物的生产工艺。
• US4772631A
  申请人：——

  公开号：US4772631A

  公开（公告）日：1988-09-20
• US4927836A
  申请人：——

  公开号：US4927836A

  公开（公告）日：1990-05-22