3-(2-chloro-4-fluorophenoxy)propyl bromide | 135062-11-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(2-chloro-4-fluorophenoxy)propyl bromide
• 英文别名: 1-(3-bromopropoxy)-2-chloro-4-fluorobenzene
• CAS: 135062-11-2
• 化学式: C₉H₉BrClFO
• 分子量: 267.525
• InChiKey: PFWDWAXEGYEOQY-UHFFFAOYSA-N

物化性质

• 沸点：
  309.4±32.0 °C(Predicted)
• 密度：
  1.521±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(2-chloro-4-fluorophenoxy)propyl bromide 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 [1-(3-(2-chloro-4-fluorophenoxy)propyl)-1,2,3-triazole-4-yl]methyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside
  参考文献：
  名称：

  甘露糖末端配体的合成和血凝抑制特性：末端苯基和甘露糖残基与三唑部分之间的接头的作用

  摘要：

  通过 Cu(I) 催化的叠氮化物-炔烃环加成反应 (CuAAC) 可以很容易地组装来自具有反向连接功能的d-甘露糖的两个三唑缀合物家族 (A, B )。甘露糖前体由 3-叠氮丙基或炔丙基糖苷配基构成，而苯基部分分别由末端叠氮基或炔丙基构成。在血凝抑制 (HAI) 试验中，A 族 ( 7a - 11a )，其中甘露糖残基和三唑环之间的接头是三个碳原子，与 B 族 ( 13a - 17a )相比，其活性增强了 3-5 倍。甲基-三唑基部分。代表配体7a，其中末端苯环被酯基取代，Cl 原子表现出最高的抑制活性，HAI 滴度为 8 μM。该化合物可能是进一步设计针对 FimH 菌毛凝集素的有效甘露糖基配体的良好候选者。

  DOI：

  10.1016/j.carres.2022.108559
• 作为产物：
  描述：

  4-氟苯酚 在 二异丁胺 、 磺酰氯 、 caesium carbonate 作用下， 生成 3-(2-chloro-4-fluorophenoxy)propyl bromide
  参考文献：
  名称：

  (2R)-2-Methylchromane-2-carboxylic acids: Discovery of selective PPARα agonists as hypolipidemic agents

  摘要：

  A SAR study was conducted on chromane-2-carboxylic acid toward selective PPAR alpha agonisim. As a result, highly potent, and selective PPAR alpha agonists were discovered. The optimized compound 43 exhibited robust lowering of total cholesterol levels in hamster and dog animal models. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.028

文献信息

• Synthesis and Characterization of 11C-Labeled Fluoroclorgyline: A Monoamine Oxidase A Specific Inhibitor for Positron Emission Tomography.
  作者：Yoshiro OHMOMO、Masahiko HIRATA、Katsuhiko MURAKAMI、Yasuhiro MAGATA、Chiaki TANAKA、Akira YOKOYAMA

  DOI：10.1248/cpb.41.1994

  日期：——

  A new radioligand for monoamine oxidase type A (MAO-A), [11C]fluoroclorgyline, was synthesized from its desmethyl precursor by N-methylation reaction using [11C]methyl iodide with a radiochemical yield of 75-85%. The radiochemical purity of the product was more than 99% and the specific radioactivity was 7.4-18.5 GBq/μmol. The in vivo tissue distribution studies of [11C]fluoroclorgyline in mice demonstrated its high initial uptake and prolonged retention in the brain, comparable to those of [11C]clorgyline. A selective interaction with MAO-A in the accumulation of [11C]fluoroclorgyline was confirmed by a competition experiment performed with the MAO-A specific inhibitor, clorgyline, and MAO-B specific inhibitor, l-deprenyl. These very desirable characteristics of [11] fluoroclorgyline suggested that its 18F labeled counterpart, [18F]fluoroclorgyline, would have great potential as a longer-lived alternative to 11C labeled clorgyline for in vivo studies of MAO-A in the human brain with positron emission tomography (PET).

  利用[11C]甲基碘通过 N-甲基化反应合成了一种新的单胺氧化酶 A 型（MAO-A）放射性配体--[11C]氟氯吉林，其放射化学收率为 75-85%。产品的放射化学纯度超过 99%，比放射性为 7.4-18.5 GBq/μmol。[11C]氟氯吉林在小鼠体内的组织分布研究表明，它在大脑中的初始摄取量高，保留时间长，与[11C]氯吉林相当。在[11C]氟氯吉林的蓄积过程中与 MAO-A 的选择性相互作用是通过与 MAO-A 特异性抑制剂氯吉林和 MAO-B 特异性抑制剂 l-deprenyl 的竞争实验来证实的。[11]氟氯吉林的这些非常理想的特性表明，其 18F 标记的对应物[18F]氟氯吉林作为 11C 标记的氯吉林的长效替代物，在利用正电子发射断层扫描（PET）对人脑中的 MAO-A 进行体内研究方面具有巨大的潜力。
• Flexible diaminodihydrotriazine inhibitors of Plasmodium falciparum dihydrofolate reductase: Binding strengths, modes of binding and their antimalarial activities
  作者：Sumalee Kamchonwongpaisan、Netnapa Charoensetakul、Choladda Srisuwannaket、Supannee Taweechai、Roonglawan Rattanajak、Jarunee Vanichtanankul、Danoo Vitsupakorn、Uthai Arwon、Chawanee Thongpanchang、Bongkoch Tarnchompoo、Tirayut Vilaivan、Yongyuth Yuthavong

  DOI：10.1016/j.ejmech.2020.112263

  日期：2020.6

  and shown to inhibit P. falciparum dihydrofolate reductase (PfDHFR) of the wild type or those carrying either single (S108N), double (C59R + S108N and A16V + S108T), triple (N51I + C59R + S108N and C59R + S108N + I164L) or quadruple (N51I + C59R + S108N + I164L) mutations, responsible for antifolate resistance. The flexibility of the side chain at position N1 has been included in the design so as to avoid

  已开发出一系列灵活的二氨基二氢三嗪或环鸟嘌呤（Cyc）类似物，并显示可抑制野生型的恶性疟原虫二氢叶酸还原酶（PfDHFR）或携带单个（S108N），携带两个（C59R + S108N和A16V + S108T），携带三个（N51I + C59R + S108N和C59R + S108N + I164L）或四倍（N51I + C59R + S108N + I164L）突变，引起抗叶酸耐药性。设计中已包括位置N1的侧链的柔性，以避免与抗性突变体的残基108的侧链发生不利的空间相互作用。许多抑制剂对突变酶的抑制常数在低纳摩尔区域。用A16V和S108N系列突变体都实现了药物结合效率的重新获得。为与突变型酶最佳相互作用而设计的某些酶抑制剂复合物的X射线研究表明，结合模式与Ki值一致。这些化合物中的许多对具有突变酶的抗性恶性疟原虫显示出优异的抗疟活性，并且对哺乳动物细胞显示出低细胞毒性，使其成为抗疟药物的进一步开发的良好候选者。
• Synthesis of fluorine and iodine analogues of clorgyline and selective inhibition of monoamine oxidase A.
  作者：Yoshiro OHMOMO、Masahiko HIRATA、Katsuhiko MURAKAMI、Yasuhiro MAGATA、Chiaki TANAKA、Akira YOKOYAMA

  DOI：10.1248/cpb.39.1038

  日期：——

  A series of fluorine and iodine analogues of clorgyline was synthesized and evaluated for inhibitory potency and selectivity toward monoamine oxidase A (MAO-A). Among them, N-[3(2, 4-dichloro-6-iodophenoxy)propyl]-N-methyl-2-propynylamine (3d), N-[3-(4-chloro-2-fluorophenoxy)propyl]-N-methyl-2-propynylamine (3f) and N-[3-(2-chloro-4-fluorophenoxy)propyl]-N-methyl-2-propynylamine (3g) were found to have high inhibitory potency and selectivity toward MAO-A comparable to those of clorgyline itself. Thus, they were considered for advanced development as radiofluorinated and radioiodinated ligands that may be useful for functional MAO-A studies in the living brain with positron emission tomography and single photon emission computer tomography.

  合成了一系列氯吉林的氟和碘类似物，并评估了其对单胺氧化酶 A (MAO-A) 的抑制效力和选择性。其中，N-[3(2,4-二氯-6-碘苯氧基)丙基]-N-甲基-2-丙炔胺(3d)、N-[3-(4-氯-2-氟苯氧基)丙基]-N发现-甲基-2-丙炔胺 (3f) 和 N-[3-(2-氯-4-氟苯氧基)丙基]-N-甲基-2-丙炔胺 (3g) 对 MAO-A 具有高抑制效力和选择性与氯吉林本身的效果相当。因此，它们被认为是作为放射性氟化和放射性碘化配体进行高级开发，可能有助于利用正电子发射断层扫描和单光子发射计算机断层扫描对活体大脑进行功能性 MAO-A 研究。
• Ohmomo Yoshiro, Hirata Masahiko, Murakami Katsuhiko, Magata Yasuhiro, Tan+, Chem. and pharm. bull, 41 (1993) N 11, S 1994- 1997
  作者：Ohmomo Yoshiro, Hirata Masahiko, Murakami Katsuhiko, Magata Yasuhiro, Tan+

  DOI：——

  日期：——
• (2R)-2-Methylchromane-2-carboxylic acids: Discovery of selective PPARα agonists as hypolipidemic agents
  作者：Hiroo Koyama、Julia K. Boueres、Daniel J. Miller、Joel P. Berger、Karen L. MacNaul、Pei-ran Wang、Marc C. Ippolito、Samuel D. Wright、Arun K. Agrawal、David E. Moller、Soumya P. Sahoo

  DOI：10.1016/j.bmcl.2005.05.028

  日期：2005.7

  A SAR study was conducted on chromane-2-carboxylic acid toward selective PPAR alpha agonisim. As a result, highly potent, and selective PPAR alpha agonists were discovered. The optimized compound 43 exhibited robust lowering of total cholesterol levels in hamster and dog animal models. (c) 2005 Elsevier Ltd. All rights reserved.