methyl <4-<2-<(2-hydroxy-3-phenoxypropyl)amino>ethoxy>phenoxy>acetate | 107332-58-1

• 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 <4-<2-<(2-hydroxy-3-phenoxypropyl)amino>ethoxy>phenoxy>acetate
• 英文别名: ICI 198,157；ICI 198157；methyl 2-p-(2-[(2-hydroxy-3-phenoxypropyl)-amino]ethoxy)phenoxyacetate；(-)-Methyl 4-[2-(2-hydroxy-3-phenoxypropylamino)ethoxy]phenoxyacetate；methyl 2-p-(2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy)phenoxyacetate；methyl 2-[4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate
• CAS: 107332-58-1
• 化学式: C₂₀H₂₅NO₆
• 分子量: 375.422
• InChiKey: XPXQYIOOPXUJDD-UHFFFAOYSA-N

物化性质

• 沸点：
  542.5±50.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  86.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl <4-<2-<(2-hydroxy-3-phenoxypropyl)amino>ethoxy>phenoxy>acetate 在 氨 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 2-p-(2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy)phenoxyacetamide
  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
• 作为产物：
  描述：

  苯基缩水甘油醚 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 溶剂黄146 、 potassium iodide 作用下， 以 甲醇 、 异丙醇 、 丙酮 为溶剂， 60.0 ℃ 、2.0 MPa 条件下， 反应 144.0h， 生成 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

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。
• Mammalian ICYP (Iodocyanopindolol) receptor and its applications
  申请人：Vetigen

  公开号：EP0848059A1

  公开（公告）日：1998-06-17

  An isolated and substantially pure mammal polypeptide different from known adrenergic, serotonine and dopamine receptors, existing at least on mammalian muscle and eosinophils membranes, for instance in rat, guinea pig and humans. The invention also relates to plasmids containing the genes coding for said polypeptide, to host cells transformed by genes coding for the above mentioned polypeptide, to nucleotide probes capable of hybridizing with the genes coding for the above mentioned polypeptide, and to polyclonal and monoclonal antibodies directed against the above mentioned polypeptide. Said polypeptide is characterized in that it contains sites such that when said sites are exposed at the surface of a cell, they are able of binding iodocyanopindolol (ICYP) under blockade of α, β1, β2, β3-AR, serotonine 5-HT1A and serotonine 5-HT1B receptors, said binding being saturable, reversible and able to be displaced by a β-adrenergic receptor agonist SM-11044 with stereoselectivity but not by isoproterenol, norepinephrine, epinephrine, serotonine, dopamine or BRL-37344, said polypeptide (1) having an apparent molecular weight of about 30-40 kDa when labeled with 125I-iodocyanopindolol after photoaffinity labeling and separation by electrophoresis and an apparent molecular weight of about 60-80 kDa in Western blot, and (2) generating a fragment having the following formula DPX1FFQHRIHX2FSIFNX3 by acidic cleavage, wherein, X1 represents S (SEQ ID N°5) or X (SEQ ID N°6), X2 represents V (SEQ ID N°6) or W (SEQ ID N°5) and X3 represents S (SEQ ID N°5) or H (SEQ ID N°6), said polypeptide being present at least on muscles and eosinophils membranes and being a non-adrenergic receptor.

  一种分离的、纯度很高的哺乳动物多肽，它不同于已知的肾上腺素能受体、血清素受体和多巴胺受体，至少存在于哺乳动物的肌肉和嗜酸性粒细胞膜上，例如存在于大鼠、豚鼠和人体内。 本发明还涉及含有上述多肽编码基因的质粒、由上述多肽编码基因转化的宿主细胞、能与上述多肽编码基因杂交的核苷酸探针以及针对上述多肽的多克隆抗体和单克隆抗体。 上述多肽的特征在于它含有这样的位点：当上述位点暴露在细胞表面时，它们能够在 α、β1、β2、β3-AR、5-羟色胺 5-HT1A 和 5-HT1B 受体的阻断下结合碘氰基吲哚洛尔（ICYP）、所述结合具有饱和性、可逆性，能被β-肾上腺素能受体激动剂 SM-11044 以立体选择性取代，但不能被异丙肾上腺素、去甲肾上腺素、肾上腺素、血清素、多巴胺或 BRL-37344 取代、所述多肽(1)在光亲和标记后用 125I-碘氰基吲哚标记并通过电泳分离时表观分子量约为 30-40 kDa，在 Western 印迹中表观分子量约为 60-80 kDa，(2)通过酸性裂解生成具有下式 DPX1FFQHRIHX2FSIFNX3 的片段、其中，X1 代表 S（SEQ ID N°5）或 X（SEQ ID N°6），X2 代表 V（SEQ ID N°6）或 W（SEQ ID N°5），X3 代表 S（SEQ ID N°5）或 H（SEQ ID N°6），所述多肽至少存在于肌肉和嗜酸性粒细胞膜上，是一种非肾上腺素能受体。
• 2-Hydroxy-3-phenoxypropyl amines
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0210849B1

  公开（公告）日：1990-08-29
• MAMMALIAN ICYP (IODOCYANOPINDOLOL)RECEPTOR AND ITS APPLICATIONS
  申请人：Dainippon Sumitomo Pharma Co., Ltd.

  公开号：EP0951548B1

  公开（公告）日：2006-02-08
• US4772631A
  申请人：——

  公开号：US4772631A

  公开（公告）日：1988-09-20