1-(2,3-epoxypropoxy)-3-fluorobenzene | 4698-94-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(2,3-epoxypropoxy)-3-fluorobenzene
• 英文别名: (2S)-3-(3-fluorophenoxy)-1,2-epoxypropane；3-fluorophenoxymethyloxirane；3-fluorophenyl glycidyl ether；2-[(3-Fluorophenoxy)methyl]oxirane
• CAS: 4698-94-6
• 化学式: C₉H₉FO₂
• 分子量: 168.168
• InChiKey: SESYYUSVZQAGGO-UHFFFAOYSA-N

物化性质

• 沸点：
  225.3±10.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  21.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2,3-epoxypropoxy)-3-fluorobenzene 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 (4-{2-[3-(3-Fluoro-phenoxy)-2-hydroxy-propylamino]-ethoxy}-phenoxy)-acetic acid methyl ester
  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：

  3-氟苯酚 、 环氧溴丙烷 在 potassium carbonate 作用下， 以 丁酮 为溶剂， 生成 1-(2,3-epoxypropoxy)-3-fluorobenzene
  参考文献：
  名称：

  Thienopyrimidines as β3-adrenoceptor agonists: Hit-to-lead optimization

  摘要：

  Resulting from a vHTS based on a pharmacophore alignment on known beta 3-adrenoceptor ligands, an aryloxypropanolamine scaffold comprising a thienopyrimidine moiety was further optimized as a human beta 3-AR agonist, yielding a lead compound with an excellent cellular activity of EC(50) = 20 pM, selectivity over h beta 1- and h beta 2- adrenoceptors and a promising safety profile. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.039

文献信息

• [EN] ANALGESIC THAT BINDS FILAMIN A<br/>[FR] ANALGÉSIQUE QUI SE LIE À LA FILAMINE A
  申请人：PAIN THERAPEUTICS INC

  公开号：WO2010051374A1

  公开（公告）日：2010-05-06

  A compound, composition and method are disclosed that can provide analgesia. A contemplated compound has a structure that corresponds to Formula A, wherein A, B, X, R1, R2, R7 and R8, and the dashed lines are defined within.

  公开了一种化合物、组合物及方法，能够提供镇痛效果。所考虑的化合物具有与式A相对应的结构，其中A、B、X、R1、R2、R7和R8以及虚线均在定义范围内。
• Studies on Agents with Vasodilator and .BETA.-Blocking Activities. II.
  作者：Toshimi SEKI、Takayuki TAKEZAKI、Rikio OHUCHI、Hiroshi OHUYABU、Yoshitaka TANIMOTO、Takashi YAMAGUCHI、Norinobu SAITOH、Tsutomu ISHIMORI、Kikuo YASUDA

  DOI：10.1248/cpb.43.247

  日期：——

  A series of phenoxypropanolamines having a hydrazinopyridazinyl moiety was synthesized. Their hypotensive and β-blocking activities were evaluated after intravenous administration of the compounds to anethetized rats.Some of them exhibited both activities. In particular, compound 20k is a candidate for clinical use due to its hypotensive activity, equal to that of hydralazine, and its β-blocking activity, 2.7-fold more potent than that of propranolol.

  一系列含有哒嗪基肼结构的苯氧丙醇胺类化合物被合成，并通过静脉注射给麻醉大鼠后评估了它们的降压和β阻断活性。其中一些化合物显示了这两种活性。特别是化合物20k，由于其降压活性与肼达嗪相当，且β阻断活性比普萘洛尔强2.7倍，因此被认为是临床应用的候选药物。
• Method of using calcilytic compounds
  申请人：NPS Pharmaceuticals, Inc.

  公开号：US06022894A1

  公开（公告）日：2000-02-08

  The present invention features calcilytic compounds. "Calcilytic compounds" refer to compounds able to inhibit calcium receptor activity. Also described are the use of calcilytic compounds to inhibit calcium receptor activity and/or achieve a beneficial effect in a patient; and techniques which can be used to obtain additional calcilytic compounds.

  本发明涉及钙受体拮抗剂化合物。"钙受体拮抗剂化合物"指的是能够抑制钙受体活性的化合物。还描述了利用钙受体拮抗剂化合物来抑制钙受体活性和/或在患者中达到有益效果的方法；以及可用于获取额外钙受体拮抗剂化合物的技术。
• Thiazolidine and oxazolidine derivatives, their preparation and their
  申请人：Sankyo Company, Limited

  公开号：US05578620A1

  公开（公告）日：1996-11-26

  Compounds of formula (I): ##STR1## and salts, esters and solyates thereof and pro-drugs therefor are useful for the treatment and/or prophylaxis of a variety of disorders, including one or more of: hyperlipemia, hyperglycemia, obesity, glucose tolerance insufficiency, insulin resistance and diabetic complications.

  公式（I）的化合物：##STR1##及其盐、酯和溶剂化合物以及其前体药物对于治疗和/或预防多种疾病非常有用，包括但不限于：高脂血症、高血糖、肥胖、葡萄糖耐量不足、胰岛素抵抗和糖尿病并发症。
• Studies on New Phosphodiesterase Inhibitors. I. Synthesis of 1-(2,3-Epoxypropoxy)-2(4)-fluorobenzenes and 1-(2-Hydroxy-3-morpholinopropoxy and Piperazino)fluorobenzene Derivatives.
  作者：Nigel R. BAKER、Nick G. BYRNE、Apollo P. ECONOMIDES、Tariq JAVED

  DOI：10.1248/cpb.43.1045

  日期：——

  A series of 1-(2, 3-epoxypropoxy)-2(4)-fluorobenzenes and their corresponding 1-(2-hydroxy-3-morpholino propoxy and piperazino)fluorobenzene derivatives (8a-f) were synthesised via a short synthetic route in good chemical yields and were evaluated for intropic and chronotropic activity in isolated guinea-pig atria preparation. The compounds act as potential phosphodiesterase (PDE) inhibitors with desirable biological activity and have considerable promise in heart therapy.

  通过简短的合成路线合成了一系列 1-(2,3-环氧丙氧基)-2(4)-氟苯及其相应的 1-(2-羟基-3-吗啉丙氧基和哌嗪基)氟苯衍生物 (8a-f)，化学收率良好。这些化合物是潜在的磷酸二酯酶（PDE）抑制剂，具有理想的生物活性，有望用于心脏治疗。