1-(4-fluorophenyl)-3-(piperidin-4-yl)-1-propanone | 76000-17-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-fluorophenyl)-3-(piperidin-4-yl)-1-propanone
• 英文别名: 1-(4-fluorophenyl)-3-(piperidin-4-yl)propan-1-one；1-(4-Fluorophenyl)-3-piperidin-4-ylpropan-1-one
• CAS: 76000-17-4
• 化学式: C₁₄H₁₈FNO
• 分子量: 235.301
• InChiKey: KRSZAIJDFCKWMS-UHFFFAOYSA-N

物化性质

• 沸点：
  352.9±12.0 °C(Predicted)
• 密度：
  1.068±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-3-(piperidin-4-yl)-1-propanone 在 sodium hydroxide 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 4-(3-(4-fluorophenyl)-3,3-(ethylenedioxy)propyl)-1-(benzyloxycarbonyl) piperidine
  参考文献：
  名称：

  1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists: modifications of the arylpropylpiperidine side chains

  摘要：

  The 4-(3-phenylprop-1-yl)piperidine moiety of the 1,3,4-trisubstituted pyrrolidine CCR5 antagonist 1 was modified with electron deficient aromatics as well as replacement of the benzylic methylene with sulfones, gem-difluoromethylenes and alcohols in an effort to balance the antiviral potency with reasonable pharmacokinetics. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00829-6
• 作为产物：
  描述：

  1-N-BOC-4-哌啶丙酸 在 N-甲基吗啉 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 为溶剂， 生成 1-(4-fluorophenyl)-3-(piperidin-4-yl)-1-propanone
  参考文献：
  名称：

  1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists: modifications of the arylpropylpiperidine side chains

  摘要：

  The 4-(3-phenylprop-1-yl)piperidine moiety of the 1,3,4-trisubstituted pyrrolidine CCR5 antagonist 1 was modified with electron deficient aromatics as well as replacement of the benzylic methylene with sulfones, gem-difluoromethylenes and alcohols in an effort to balance the antiviral potency with reasonable pharmacokinetics. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00829-6

文献信息

• The novel therapeutic strategy of vilazodone-donepezil chimeras as potent triple-target ligands for the potential treatment of Alzheimer's disease with comorbid depression
  作者：Xiaokang Li、Jinwen Li、Yunyuan Huang、Qi Gong、Yan Fu、Yixiang Xu、Junyang Huang、Haolan You、Dong Zhang、Dan Zhang、Fei Mao、Jin Zhu、Huan Wang、Haiyan Zhang、Jian Li

  DOI：10.1016/j.ejmech.2021.114045

  日期：2022.2

  pharmacophores of the antidepressant vilazodone (5-HT1A receptor partial agonist and serotonin transporter inhibitor) and the anti-AD drug donepezil (acetylcholinesterase inhibitor) together to develop a series of multi-target-directed ligands for potential therapy of the comorbidity of AD and depression. Accordingly, 55 vilazodone-donepezil chimeric derivatives were designed and synthesized, and their triple-target

  抑郁症是阿尔茨海默病 (AD) 最常见的共病精神症状之一，迄今为止还没有专门为此目的批准的有效药物。在此，我们提出了一种新的治疗策略，将抗抑郁药维拉佐酮（5-HT 1A受体部分激动剂和5-羟色胺转运蛋白抑制剂）和抗AD药物多奈哌齐（乙酰胆碱酯酶抑制剂）的关键药效​​团结合在一起，开发了一系列多靶点。用于潜在治疗 AD 和抑郁症共病的定向配体。因此，设计并合成了 55 种维拉佐酮-多奈哌齐嵌合衍生物，以及它们对乙酰胆碱酯酶 5-HT 1A的三靶点活性。受体和血清素转运蛋白进行了系统评估。其中，化合物5在体外表现出很强的三靶点生物活性、低hERG钾通道抑制和可接受的脑分布。重要的是，口服 5 mg/kg 的化合物5二盐酸盐可显着减轻小鼠模型的抑郁症状并改善认知功能障碍。简而言之，这些结果突出了维拉佐酮-多奈哌齐嵌合体作为治疗 AD 和抑郁症合并症的前瞻性治疗方法。
• Central Cholinergic Agents. IV. Synthesis and Acetylcholinesterase Inhibitory Activities of .OMEGA.-(N-Ethyl-N-(phenylmethyl)amino)-1-phenyl-1-alkanones and Their Analogues with Partial Conformational Restriction.
  作者：Yuji ISHIHARA、Masaomi MIYAMOTO、Takahiro NAKAYAMA、Giichi GOTO

  DOI：10.1248/cpb.41.529

  日期：——

  Inhibitors of acetylcholinesterase (AChE) have been designed based on a working hypothesis of the enzyme's active site. These compounds were tested for their inhibitory activities on AChE and ω-[N-ethyl-N-(phenylmethyl)amino]-1-phenyl-1-alkanones (3) were found to be potent inhibitors. Various analogues of 3 were prepared to study the effect on AChE inhibition of partial restriction of conformation. Compounds with potent AChE inhibition were further evaluated in terms of central selectivity : the ratio of central action (ameliorationg effect on scopolamine-induced memory impairment using a T-maze alternation task) to peripheral action.

  乙酰胆碱酯酶（AChE）抑制剂的设计是基于酶的活性位点的工作假设。这些化合物被测试了其对AChE的抑制活性，ω-[N-乙基-N-(苯甲基)氨基]-1-苯基-1-烷酮（3）被发现是有效的抑制剂。为了研究构象部分限制对AChE抑制的影响，制备了3的各种类似物。具有强效AChE抑制的化合物进一步评估了其中心选择性：中心作用（在T型迷宫交替任务中改善斯科波拉明诱导的记忆损害的效果）与外周作用的比率。
• US4294841A
  申请人：——

  公开号：US4294841A

  公开（公告）日：1981-10-13
• 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists: modifications of the arylpropylpiperidine side chains
  作者：Christopher L. Lynch、Christopher A. Willoughby、Jeffrey J. Hale、Edward J. Holson、Richard J. Budhu、Amy L. Gentry、Keith G. Rosauer、Charles G. Caldwell、Ping Chen、Sander G. Mills、Malcolm MacCoss、Scott Berk、Liya Chen、Kevin T. Chapman、Lorraine Malkowitz、Martin S. Springer、Sandra L. Gould、Julie A. DeMartino、Salvatore J. Siciliano、Margaret A. Cascieri、Anthony Carella、Gwen Carver、Karen Holmes、William A. Schleif、Renee Danzeisen、Daria Hazuda、Joseph Kessler、Janet Lineberger、Michael Miller、Emilio A. Emini

  DOI：10.1016/s0960-894x(02)00829-6

  日期：2003.1

  The 4-(3-phenylprop-1-yl)piperidine moiety of the 1,3,4-trisubstituted pyrrolidine CCR5 antagonist 1 was modified with electron deficient aromatics as well as replacement of the benzylic methylene with sulfones, gem-difluoromethylenes and alcohols in an effort to balance the antiviral potency with reasonable pharmacokinetics. (C) 2002 Elsevier Science Ltd. All rights reserved.