(4-(4-iodophenyl)piperazin-1-yl)(morpholino)methanone | 1548115-92-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (4-(4-iodophenyl)piperazin-1-yl)(morpholino)methanone
• 英文别名: [4-(4-Iodophenyl)piperazin-1-yl]-morpholin-4-ylmethanone；[4-(4-iodophenyl)piperazin-1-yl]-morpholin-4-ylmethanone
• CAS: 1548115-92-9
• 化学式: C₁₅H₂₀IN₃O₂
• 分子量: 401.247
• InChiKey: ITUWDETWNLXHDB-UHFFFAOYSA-N

物化性质

• 熔点：
  151-153 °C
• 沸点：
  501.8±50.0 °C(predicted)
• 密度：
  1.600±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  36
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-(4-iodophenyl)piperazin-1-yl)(morpholino)methanone 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 (4-(4-ethynylphenyl)piperazin-1-yl)(morpholino)methanone
  参考文献：
  名称：

  Morpholylureas are a new class of potent and selective inhibitors of the type 5 17-β-hydroxysteroid dehydrogenase (AKR1C3)

  摘要：

  Inhibitors of the aldo-keto reductase enzyme AKR1C3 are of interest as potential drugs for leukemia and hormone-related cancers. A series of non-carboxylate morpholino(phenylpiperazin-1-yl)methanones were prepared by palladium-catalysed coupling of substituted phenyl or pyridyl bromides with the known morpholino(piperazin-1-yl)methanone, and shown to be potent (IC50 similar to 100 nM) and very isoform-selective inhibitors of AKR1C3. Lipophilic electron-withdrawing substituents on the phenyl ring were positive for activity, as was an H-bond acceptor on the other terminal ring, and the ketone moiety (as a urea) was essential. These structure-activity relationships are consistent with an X-ray structure of a representative compound bound in the AKR1C3 active site, which showed H-bonding between the carbonyl oxygen of the drug and Tyr55 and His117 in the 'oxyanion hole' of the enzyme, with the piperazine bridging unit providing the correct twist to allow the terminal benzene ring to occupy the lipophilic pocket and align with Phe311. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.050
• 作为产物：
  描述：

  吗啉-4-基哌嗪-1-基甲酮 在 copper(l) iodide 、 palladium diacetate 、 (1S,2S)-(+)-N,N'-二甲基环己烷-1,2-二胺 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium iodide 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 64.0h， 生成 (4-(4-iodophenyl)piperazin-1-yl)(morpholino)methanone
  参考文献：
  名称：

  Morpholylureas are a new class of potent and selective inhibitors of the type 5 17-β-hydroxysteroid dehydrogenase (AKR1C3)

  摘要：

  Inhibitors of the aldo-keto reductase enzyme AKR1C3 are of interest as potential drugs for leukemia and hormone-related cancers. A series of non-carboxylate morpholino(phenylpiperazin-1-yl)methanones were prepared by palladium-catalysed coupling of substituted phenyl or pyridyl bromides with the known morpholino(piperazin-1-yl)methanone, and shown to be potent (IC50 similar to 100 nM) and very isoform-selective inhibitors of AKR1C3. Lipophilic electron-withdrawing substituents on the phenyl ring were positive for activity, as was an H-bond acceptor on the other terminal ring, and the ketone moiety (as a urea) was essential. These structure-activity relationships are consistent with an X-ray structure of a representative compound bound in the AKR1C3 active site, which showed H-bonding between the carbonyl oxygen of the drug and Tyr55 and His117 in the 'oxyanion hole' of the enzyme, with the piperazine bridging unit providing the correct twist to allow the terminal benzene ring to occupy the lipophilic pocket and align with Phe311. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.050

文献信息

• Morpholylureas are a new class of potent and selective inhibitors of the type 5 17-β-hydroxysteroid dehydrogenase (AKR1C3)
  作者：Jack U. Flanagan、Graham J. Atwell、Daniel M. Heinrich、Darby G. Brooke、Shevan Silva、Laurent J.M. Rigoreau、Elisabeth Trivier、Andrew P. Turnbull、Tony Raynham、Stephen M.F. Jamieson、William A. Denny

  DOI：10.1016/j.bmc.2013.12.050

  日期：2014.2

  Inhibitors of the aldo-keto reductase enzyme AKR1C3 are of interest as potential drugs for leukemia and hormone-related cancers. A series of non-carboxylate morpholino(phenylpiperazin-1-yl)methanones were prepared by palladium-catalysed coupling of substituted phenyl or pyridyl bromides with the known morpholino(piperazin-1-yl)methanone, and shown to be potent (IC50 similar to 100 nM) and very isoform-selective inhibitors of AKR1C3. Lipophilic electron-withdrawing substituents on the phenyl ring were positive for activity, as was an H-bond acceptor on the other terminal ring, and the ketone moiety (as a urea) was essential. These structure-activity relationships are consistent with an X-ray structure of a representative compound bound in the AKR1C3 active site, which showed H-bonding between the carbonyl oxygen of the drug and Tyr55 and His117 in the 'oxyanion hole' of the enzyme, with the piperazine bridging unit providing the correct twist to allow the terminal benzene ring to occupy the lipophilic pocket and align with Phe311. (C) 2013 Elsevier Ltd. All rights reserved.