4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-1-phenylbutan-1-one | 31293-71-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-1-phenylbutan-1-one
• 英文别名: SGT536；1-(3-Benzoyl-propyl)-4-(4-chlor-phenyl)-piperidin-4-ol；1-<3-Benzoyl-propyl>-4-<4-chlor-phenyl>-piperidin-4-ol；VUF 5666；4-[4-(4-chloro-phenyl)-4-hydroxy-piperidino]-1-phenyl-butan-1-one；4-[4-(4-Chlor-phenyl)-4-hydroxy-piperidino]-1-phenyl-butan-1-on；4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-phenyl-butan-1-one；4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-phenylbutan-1-one
• CAS: 31293-71-7
• 化学式: C₂₁H₂₄ClNO₂
• 分子量: 357.88
• InChiKey: XMYBCDHWKUBJDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(3-chloropropyl)-2-phenyl-[1,3]dioxolane 在 盐酸 、 sodium carbonate 、 sodium iodide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 2.0h， 生成 4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-1-phenylbutan-1-one
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of the First Nonpeptidergic Inverse Agonists for the Human Cytomegalovirus Encoded Chemokine Receptor US28

  摘要：

  US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 {5-(4-(4-chlorophenyl)-4-hydroxy-piperidin-1-yl)-2,2-diphenylpentanenitrile} as the first reported nonpeptidergic inverse agonist for a viral-encoded chemokine receptor. Interestingly, this compound is able to partially inhibit the viral entry of HIV-1. In this study we describe the synthesis of 1 and several of its analogues and unique structure-activity relationships for this first class of small-molecule ligands for the chemokine receptor US28. Moreover, the compounds have been pharmacologically characterized as inverse agonists on US28. By modification of lead structure 1, it is shown that a 4-phenylpiperidine moiety is essential for affinity and activity. Other structural features of 1 are shown to be of less importance. These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection.

  DOI：

  10.1021/jm050418d

文献信息

• Structure–Kinetic Profiling of Haloperidol Analogues at the Human Dopamine D₂ Receptor
  作者：Tim J. Fyfe、Barrie Kellam、David A. Sykes、Ben Capuano、Peter J. Scammells、J. Robert Lane、Steven J. Charlton、Shailesh N. Mistry

  DOI：10.1021/acs.jmedchem.9b00864

  日期：2019.11.14

  a typical antipsychotic drug (APD) associated with an increased risk of extrapyramidal side effects (EPSs) and hyperprolactinemia relative to atypical APDs such as clozapine. Both drugs are dopamine D2 receptor (D2R) antagonists, with contrasting kinetic profiles. Haloperidol displays fast association/slow dissociation at the D2R, whereas clozapine exhibits relatively slow association/fast dissociation

  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。
• Antifungal Compositions
  申请人：University of Kentucky Research Foundation

  公开号：US20190015400A1

  公开（公告）日：2019-01-17

  Provided herein are antifungal compositions and methods of use thereof. The antifungal compositions include an antifungal agent and an antipsychotic agent or an antihistamine. The methods of use thereof include administering a composition including an antifungal agent and an antipsychotic or an antihistamine to a plant or animal in need thereof.

  本文提供了抗真菌组合物及其使用方法。抗真菌组合物包括抗真菌剂和抗精神病药物或抗组胺剂。其使用方法包括向需要的植物或动物施用包含抗真菌剂和抗精神病药物或抗组胺剂的组合物。
• Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis from <i>Mycobacterium tuberculosis</i> to overcome kanamycin resistance
  作者：Ankita Punetha、Keith D. Green、Atefeh Garzan、Nishad Thamban Chandrika、Melisa J. Willby、Allan H. Pang、Caixia Hou、Selina Y. L. Holbrook、Kyle Krieger、James E. Posey、Tanya Parish、Oleg V. Tsodikov、Sylvie Garneau-Tsodikova

  DOI：10.1039/d1md00239b

  日期：——

  structure of the Eis-haloperidol (1) complex, which guided synthesis of 34 analogues. The structure–activity relationship study showed that in addition to haloperidol (1), eight analogues, some of which were smaller than 1, potently inhibited Eis (IC50 ≤ 1 μM). Crystal structures of Eis in complexes with three potent analogues and droperidol (DPD), an antiemetic and antipsychotic, were determined. Three

  结核病 (TB) 由结核分枝杆菌( Mtb ) 引起，是一种致命的细菌性疾病。Mtb的耐药菌株使根除结核病成为一项艰巨的任务。Mtb过度表达增强的细胞内存活 (Eis) 蛋白赋予了对二线抗生素卡那霉素 (KAN) 的抗性。Eis 是一种乙酰转移酶，可将 KAN 乙酰​​化，使其抗菌功能失活。开发 Eis 抑制剂作为 KAN 辅助治疗剂是预防和克服 KAN 耐药性的一条有吸引力的途径。我们发现抗精神病药物氟哌啶醇 (HPD, 1 ) 是一种有效的 Eis 抑制剂，IC 50= 0.39 ± 0.08 μM。我们确定了 Eis-氟哌啶醇 ( 1 ) 复合物的晶体结构，该复合物指导了 34 种类似物的合成。构效关系研究表明，除氟哌啶醇 ( 1 ) 外，还有 8 种类似物，其中一些小于1，可有效抑制 Eis (IC 50 ≤ 1 μM)。确定了 Eis 与三种强效类似物和氟哌利多 (DPD)（一种
• EIS INHIBITORS
  申请人：University of Kentucky Research Foundation

  公开号：US20180162867A1

  公开（公告）日：2018-06-14

  Compounds and compositions are disclosed, which are useful as inhibitors of acetyltransferase Eis, a mediator of kanamycin resistance in Mycobacterium tuberculosis.

  揭示了作为乙酰转移酶Eis抑制剂的化合物和组合物，该酶是结核分枝杆菌中卡那霉素抗性的介质。
• SUBSTITUTED BUTYROPHENONE DERIVATIVES
  申请人：Seeman Philip

  公开号：US20100004289A1

  公开（公告）日：2010-01-07

  The present invention relates to a central nervous system-acting substituted butyrophenones. These compounds are useful in antipsychotic medications for psychosis, including schizophrenia, but especially for L-DOPA-induced psychosis, while having low or no risk of eliciting extrapyramidal side effects, hyperprolactinemia or tardive dyskinesia.

  本发明涉及中枢神经系统作用的替代丁酰苯酮。这些化合物在治疗精神病药物中具有用途，包括精神分裂症，但特别适用于L-DOPA诱导的精神病，同时具有低或无诱发锥体外系副作用，高催乳素血症或迟发性运动障碍的风险。