3-((4-fluorophenyl)-thio)propyl methanesulfonate | 1357348-83-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 3-((4-fluorophenyl)-thio)propyl methanesulfonate
• 英文别名: 3-(4-Fluorophenyl)sulfanylpropyl methanesulfonate；3-(4-fluorophenyl)sulfanylpropyl methanesulfonate
• CAS: 1357348-83-4
• 化学式: C₁₀H₁₃FO₃S₂
• 分子量: 264.342
• InChiKey: ICZAZGVCTZYBAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  77
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-嘧啶基)哌嗪 、 3-((4-fluorophenyl)-thio)propyl methanesulfonate 在 potassium carbonate 、 potassium iodide 作用下， 以 乙二醇二甲醚 为溶剂， 反应 12.0h， 生成 2-(4-(3-((4-fluorophenyl)thio)propyl)piperazin-1-yl)pyrimidine
  参考文献：
  名称：

  Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents

  摘要：

  Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contributes to changes in binding to the receptors of interest. This strategy has resulted in the identification of several new agents, compounds 16, 18, 19, 23, 24 and 25, with binding profiles which satisfy our stated criteria for agents to act as potential atypical antipsychotics. This research demonstrates that haloperidol can serve as a useful lead in the identification and design of new agents that target multiple receptors associated with antipsychotic pharmacology. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2011.12.019
• 作为产物：
  描述：

  对氟苯硫酚 在 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 13.0h， 生成 3-((4-fluorophenyl)-thio)propyl methanesulfonate
  参考文献：
  名称：

  氟哌啶醇类似物在人多巴胺D2受体上的结构动力学分析。

  摘要：

  氟哌啶醇是一种典型的抗精神病药物（APD），与非典型APD（例如氯氮平）相比，其锥体束外副作用（EPS）和高泌乳素血症的风险增加。两种药物都是多巴胺D 2受体（D 2 R）拮抗剂，具有相反的动力学特征。氟哌啶醇在D 2 R处显示快速缔合/缓慢解离，而氯氮平显示相对较慢的缔合/快速解离。最近，我们提供了证据，从D 2 R缓慢解离可预测高泌乳素血症，而快速结合可预测EPS。不幸的是，氯氮平可引起严重的副作用，而与D 2 R作用无关。我们的结果表明D 2的最佳动力学曲线避免EPS的R拮抗剂APD。为了开始研究该假设，我们进行了氟哌啶醇的结构动力学关系研究，并发现微妙的结构修饰会显着改变结合动力学速率常数，从而提供具有氯氮平样动力学特征的化合物。因此，这些动力学参数的优化可以允许开发基于氟哌啶醇支架的具有改善的副作用特征的新型APD。

  DOI：

  10.1021/acs.jmedchem.9b00864

文献信息

• Novel cyclic amide derivatives
  申请人：——

  公开号：US20030212094A1

  公开（公告）日：2003-11-13

  Novel compounds represented by the following formula (I) that act as a ligand to sigma receptor/binding cite and a medicament comprising the same as an active ingredient: 1 wherein X represents an alkyl group, an aryl group, a heterocyclic group or the like; Q represents a group represented by —CH 2 —, —CO—, —O—, —CH(OR 7 )— or the like wherein R 7 represents a hydrogen atom, an alkyl group or the like; n represents an integer of from 0 to 5; R 1 and R 2 each represent a hydrogen atom, an alkyl group or the like; B represents either of the following groups: 2 wherein R 3 , R 4 , R 5 , and R 6 each represent a hydrogen atom, a halogen atom, an alkoxyl group or the like; m represents 1 or 2; and the ring of: 3 represents an aromatic heterocyclic ring.

  以下公式（I）表示的新化合物作为sigma受体/结合位点的配体，并包括作为活性成分的药物： 其中X代表烷基、芳基、杂环基或类似基团；Q代表由—CH 2 —、—CO—、—O—、—CH(OR 7 )—或类似基团表示的基团，其中R 7 代表氢原子、烷基或类似基团；n代表从0到5的整数；R 1 和R 2 各自代表氢原子、烷基或类似基团；B代表以下任一基团： 其中R 3 、R 4 、R 5 和R 6 各自代表氢原子、卤素原子、烷氧基或类似基团；m代表1或2；以及： 代表芳香杂环环。
• NOVEL CYCLIC AMIDE DERIVATIVES
  申请人：Mitsubishi Pharma Corporation

  公开号：EP1260512A1

  公开（公告）日：2002-11-27

  Novel compounds represented by the following formula (I) that act as a ligand to sigma receptor/binding cite and a medicament comprising the same as an active ingredient: wherein X represents an alkyl group, an aryl group, a heterocyclic group or the like; Q represents a group represented by -CH2-, -CO-, -O-, -CH(OR7)- or the like wherein R7 represents a hydrogen atom, an alkyl group or the like; n represents an integer of from 0 to 5; R1 and R2 each represent a hydrogen atom, an alkyl group or the like; B represents either of the following groups: wherein R3, R4, R5, and R6 each represent a hydrogen atom, a halogen atom, an alkoxyl group or the like; m represents 1 or 2; and the ring of: represents an aromatic heterocyclic ring.

  由下式(I)代表的可作为σ受体/结合引物的配体的新型化合物以及以其为有效成分的药物： 其中 X 代表烷基、芳基、杂环基或类似基团； Q 代表-CH2-、-CO-、-O-、-CH(OR7)-或类似基团，其中 R7 代表氢原子、烷基或类似基团； n 代表 0 至 5 的整数； R1 和 R2 各自代表氢原子、烷基或类似基团； B 代表以下任一基团： 其中 R3、R4、R5 和 R6 各自代表氢原子、卤素原子、烷氧基或类似基团；m 代表 1 或 2；环的： 代表芳香杂环。
• Structure–activity relationship studies of SYA 013, a homopiperazine analog of haloperidol
  作者：Kwakye Peprah、Xue Y. Zhu、Suresh V.K. Eyunni、Jagan R. Etukala、Vincent Setola、Bryan L. Roth、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2012.01.022

  日期：2012.3

  Structure-activity relationship studies on 4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl) butan-1-one (SYA 013), a homopiperazine analog of haloperidol has resulted in an understanding of the effect of structural modifications on binding affinity at dopamine and serotonin receptor subtypes. Further exploration, using bioisosteric replacement strategies has led to the identification of several new agents including compounds 7, 8, 11 and 12 which satisfy the initial criteria for further exploration as new antipsychotic agents. In addition, compound 18, a D-3 selective tropanol, has been identified as having the potential for further optimization into a useful drug which may combat neuropsychiatric diseases. Published by Elsevier Ltd.
• Identification of a new selective dopamine D4 receptor ligand
  作者：Dinithia Sampson、Xue Y. Zhu、Suresh V.K. Eyunni、Jagan R. Etukala、Edward Ofori、Barbara Bricker、Nazarius S. Lamango、Vincent Setola、Bryan L. Roth、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2014.04.026

  日期：2014.6

  The dopamine D-4 receptor has been shown to play key roles in certain CNS pathologies including addiction to cigarette smoking. Thus, selective D-4 ligands may be useful in treating some of these conditions. Previous studies in our laboratory have indicated that the piperazine analog of haloperidol exhibits selective and increased affinity to the DAD(4) receptor subtype, in comparison to its piperidine analog. This led to further exploration of the piperazine moiety to identify new agents that are selective at the D-4 receptor. Compound 27 (KiD4 = 0.84 nM) was the most potent of the compounds tested. However, it only had moderate selectivity for the D-4 receptor. Compound 28 (KiD4 = 3.9 nM) while not as potent, was more discriminatory for the D-4 receptor subtype. In fact, compound 28 has little or no binding affinity to any of the other four DA receptor subtypes. In addition, of the 23 CNS receptors evaluated, only two, 5HT(1A)R and 5HT(2B)R, have binding affinity constants better than 100 nM (K-i < 100 nM). Compound 28 is a potentially useful D-4-selective ligand for probing disease treatments involving the D-4 receptor, such as assisting smoking cessation, reversing cognitive deficits in schizophrenia and treating erectile dysfunction. Thus, further optimization, functional characterization and evaluation in animal models may be warranted. Published by Elsevier Ltd.
• SYA 013 analogs as moderately selective sigma-2 (σ2) ligands: Structure-affinity relationship studies
  作者：Lamya Al-Ghanim、Xue Y. Zhu、Gladys Asong、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2019.01.035

  日期：2019.6

  Several lines of evidence suggest that selective sigma-2 (sigma(2)) ligands might be useful for the treatment of solid tumors. However, very few selective sigma(2) ligands have been identified. This study was aimed at identifying new selective sigma(2) receptor ligands using a previously identified agent, SYA 013 as a lead. Four groups, homopiperazine, piperazine, tropane and selected oxime analogs of the homopiperazines were identified, synthesized and subsequently screened at the sigma(1) and sigma(2) receptors. The results demonstrate that these scaffolds can be modified to obtain selective sigma(2) receptor ligands. 1-(5-Chloropyridin-2-yl)-4-(3-((4-fluorophenyl)thio)propyl)-1,4-diazepane, 7 and 3-(4-chlorophenyl)-8-(3-((2-fluorophenyl)thio)propyl)-8-azabicyclo[ 3.2.1]octan-3-ol, 21 were identified as the highest binding affinity ligands (sigma(2)Ki = 2.2 nM) and (4-(4-(5-chloropyridin-2-yl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl)-butan-1-one oxime, 22 as a high affinity and the most selective ligand for the sigma(2) receptor (sigma(1)Ki/sigma(2)Ki = 41.8).