(S)-dihydrohaloperidol | 136271-61-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (S)-dihydrohaloperidol
• 英文别名: (1S)-(-)-4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-hydroxybutyl]piperidin-4-ol；(S)-(-)-4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-hydroxybutyl]piperidin-4-ol；(S)-(-)-haloperidol metabolite II；(-)-Dihydrohaloperidol；Dihydrohaloperidol, (S)-；4-(4-chlorophenyl)-1-[(4S)-4-(4-fluorophenyl)-4-hydroxybutyl]piperidin-4-ol
• CAS: 136271-61-9
• 化学式: C₂₁H₂₅ClFNO₂
• 分子量: 377.886
• InChiKey: WNZBBTJFOIOEMP-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

已减少的氟哌啶醇已知的人类代谢物包括CPHP和氟哌啶醇。

Reduced_haloperidol has known human metabolites that include CPHP and haloperidol.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  4-苯基丁酰氯 、 (S)-dihydrohaloperidol 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 (1S)-(-)-4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butyl 4-phenylbutanoate
  参考文献：
  名称：

  Haloperidol metabolite II prodrug: Asymmetric synthesis and biological evaluation on rat C6 glioma cells

  摘要：

  In a previous work we reported the antiproliferative effects of (+/-)-MRJF4, a novel haloperidol metabolite II (HP-mII) (a sigma-1 antagonist and sigma-2 agonist) prodrug, obtained through conjugation to 4-phenylbutyric acid (PhBA) [a histone deacetylase inhibitor (HDACi)] via an ester bond. As a continuation of this work, here we report the asymmetric synthesis of compounds (R)-(+)-MRJF4 and (S)(-)-MRJF4 and the evaluation of their biological activity on rat C6 glioma cells, derived from glioblastoma multiforme (GBM), which is the most common and deadliest central nervous system (CNS) invasive malignancy. Favourable physicochemical properties, high permeability in the parallel artificial membrane permeability assay (PAMPA), good enzymatic and chemical stability, in vivo anticancer activity, associated with the capacity to reduce cell viability and to increase cell death by apoptosis, render compound (R)-(+)-MRJF4 a promising candidate for the development of a useful therapeutic for gliomas therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.012
• 作为产物：
  描述：

  4-氯-4'-氟苯丁酮 在 potassium hydrogencarbonate 、 (-)-diisopinocamphenylborane chloride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 (S)-dihydrohaloperidol
  参考文献：
  名称：

  氟哌啶醇代谢物 II 丙戊酸酯 (S)-(−)-MRJF22：作为潜在多功能药物治疗葡萄膜黑色素瘤的初步研究

  摘要：

  血管生成和血管内皮生长因子 (VEGF) 水平的增加导致葡萄膜黑色素瘤 (UM) 的转移和死亡率增加，这是一种成人眼部的侵袭性恶性肿瘤。(±)-MRJF22是与组蛋白去乙酰化酶 (HDAC) 抑制剂丙戊酸偶联的 σ (σ) 配体氟哌啶醇代谢物 II 的前药，之前已证明具有良好的抗血管生成活性。在此，进行了(R)-(+)-MRJF22和(S)-(-)-MRJF22的不对称合成，以研究它们对(±)-MRJF22的贡献人视网膜内皮细胞 (HREC) 的抗血管生成作用，并评估其在原发性人葡萄膜黑色素瘤 (UM) 92-1 细胞系中的治疗潜力。虽然两种对映异构体显示出与外消旋混合物几乎相同的降低细胞活力的能力，但(S)-(-)-MRJF22在内皮细胞和肿瘤细胞中表现出最高的抗迁移作用。鉴于细胞运动对癌症进展的基本贡献，(S)-(-)-MRJF22可能代表 UM 患者新型抗转移治疗的有希望的候选者。

  DOI：

  10.1021/acs.jmedchem.1c00995

文献信息

• Haloperidol Metabolite II Valproate Ester (<i>S</i>)-(−)-MRJF22: Preliminary Studies as a Potential Multifunctional Agent Against Uveal Melanoma
  作者：Carla Barbaraci、Giovanni Giurdanella、Claudia Giovanna Leotta、Anna Longo、Emanuele Amata、Maria Dichiara、Lorella Pasquinucci、Rita Turnaturi、Orazio Prezzavento、Ivana Cacciatore、Elisa Zuccarello、Gabriella Lupo、Giovanni Mario Pitari、Carmelina Daniela Anfuso、Agostino Marrazzo

  DOI：10.1021/acs.jmedchem.1c00995

  日期：2021.9.23

  metabolite II conjugated with the histone deacetylase (HDAC) inhibitor valproic acid, has previously demonstrated a promising antiangiogenic activity. Herein, the asymmetric synthesis of (R)-(+)-MRJF22 and (S)-(−)-MRJF22 was performed to investigate their contribution to (±)-MRJF22 antiangiogenic effects in human retinal endothelial cells (HREC) and to assess their therapeutic potential in primary

  血管生成和血管内皮生长因子 (VEGF) 水平的增加导致葡萄膜黑色素瘤 (UM) 的转移和死亡率增加，这是一种成人眼部的侵袭性恶性肿瘤。(±)-MRJF22是与组蛋白去乙酰化酶 (HDAC) 抑制剂丙戊酸偶联的 σ (σ) 配体氟哌啶醇代谢物 II 的前药，之前已证明具有良好的抗血管生成活性。在此，进行了(R)-(+)-MRJF22和(S)-(-)-MRJF22的不对称合成，以研究它们对(±)-MRJF22的贡献人视网膜内皮细胞 (HREC) 的抗血管生成作用，并评估其在原发性人葡萄膜黑色素瘤 (UM) 92-1 细胞系中的治疗潜力。虽然两种对映异构体显示出与外消旋混合物几乎相同的降低细胞活力的能力，但(S)-(-)-MRJF22在内皮细胞和肿瘤细胞中表现出最高的抗迁移作用。鉴于细胞运动对癌症进展的基本贡献，(S)-(-)-MRJF22可能代表 UM 患者新型抗转移治疗的有希望的候选者。
• Haloperidol metabolite II prodrug: Asymmetric synthesis and biological evaluation on rat C6 glioma cells
  作者：Piera Sozio、Jole Fiorito、Viviana Di Giacomo、Antonio Di Stefano、Lisa Marinelli、Ivana Cacciatore、Amelia Cataldi、Stephanie Pacella、Hasan Turkez、Carmela Parenti、Antonio Rescifina、Agostino Marrazzo

  DOI：10.1016/j.ejmech.2014.11.012

  日期：2015.1

  In a previous work we reported the antiproliferative effects of (+/-)-MRJF4, a novel haloperidol metabolite II (HP-mII) (a sigma-1 antagonist and sigma-2 agonist) prodrug, obtained through conjugation to 4-phenylbutyric acid (PhBA) [a histone deacetylase inhibitor (HDACi)] via an ester bond. As a continuation of this work, here we report the asymmetric synthesis of compounds (R)-(+)-MRJF4 and (S)(-)-MRJF4 and the evaluation of their biological activity on rat C6 glioma cells, derived from glioblastoma multiforme (GBM), which is the most common and deadliest central nervous system (CNS) invasive malignancy. Favourable physicochemical properties, high permeability in the parallel artificial membrane permeability assay (PAMPA), good enzymatic and chemical stability, in vivo anticancer activity, associated with the capacity to reduce cell viability and to increase cell death by apoptosis, render compound (R)-(+)-MRJF4 a promising candidate for the development of a useful therapeutic for gliomas therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.