4-(4-氟苄基)哌啶盐酸盐

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-(4-氟苄基)哌啶盐酸盐
• 中文别名: 4-(4-氟苄基)哌啶
• 英文名称: 4-(4-fluorobenzyl)piperidine hydrochloride
• 英文别名: 4-[(4-Fluorophenyl)methyl]piperidin-1-ium;chloride；4-[(4-fluorophenyl)methyl]piperidin-1-ium;chloride
• 化学式: C₁₂H₁₆FN*ClH
• 分子量: 229.725
• InChiKey: OJKWWANXBGLGQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.79
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  12
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(4-氟苄基)哌啶盐酸盐 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 4.2h， 生成 Co-111103
  参考文献：
  名称：

  4-Hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine:  A Novel, Potent, and Selective NR1/2B NMDA Receptor Antagonist

  摘要：

  A structure-based search and screen of our compound library identified N-(2-phenoxyethyl)4-benzylpiperidine (8) as a novel N-methyl-D-aspartate (NMDA) receptor antagonist that has high selectivity for the NR1/2B subunit combination (IC50 = 0.63 mu M). We report on the optimization of this lead compound in terms of potency, side effect liability, and in vivo activity. Potency was assayed by electrical recordings in Xenopus oocytes expressing cloned rat NMDA receptors. Side effect liability was assessed by measuring affinity for alpha(1)-adrenergic receptors and inhibition of neuronal K+ channels. Central bioavailability was gauged indirectly by determining anticonvulsant activity in a mouse maximal electroshock (MES) assay. Making progressive modifications to 8, a hydroxyl substituent on the phenyl ring para to the oxyethyl tether (10a) resulted in a similar to 25-fold increase in NR1A/2B potency (IC50 = 0.025 mu M). p-Methyl substitution on the benzyl ring (10b) produced a similar to 3-fold increase in MES activity (ED50 = 0.7 mg/kg iv). Introduction of a second hydroxyl group into the C-4 position on the piperidine ring (10e) resulted in a substantial decrease in affinity for alpha(1) receptors and reduction in inhibition of Kf channels with only a modest decrease in NR1A/2B and MES potencies. Among the compounds described, 10e (4-hydroxy-N-[2-(4-hydroxyphenoxy)ethyl]-4-(methylbenzyl)piperidine, Co 101244/PD 174494) had the optimum pharmacological profile and was selected for further biological evaluation.

  DOI：

  10.1021/jm990246i
• 作为产物：
  描述：

  tert-butyl 4-(4-fluorobenzylidene)piperidine-1-carboxylate 在 盐酸 、 palladium 10% on activated carbon 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 生成 4-(4-氟苄基)哌啶盐酸盐
  参考文献：
  名称：

  HEC-866及其类似物治疗特发性肺纤维化的进展

  摘要：

  特发性肺纤维化 (IPF) 是一种慢性进行性肺病，典型的生存时间在三到五年之间。两种药物吡非尼酮和尼达尼布已被批准用于治疗 IPF，但疗效有限。因此，开发治疗IPF的新药是迫切的医疗需求。在本文中，我们报告了一系列口服活性 pyrimidin-4(3 H )-one 类似物的发现，这些类似物在体外试验中表现出有效的活性。其中，HEC-866 在大鼠 IPF 模型中显示出良好的疗效。由于 HEC-866 还具有良好的口服生物利用度、较长的半衰期和良好的长期安全性，因此被选中进行进一步的临床评估。

  DOI：

  10.1039/d1md00023c
• 作为试剂：
  描述：

  、 4-(4-氟苄基)哌啶盐酸盐 在 4-(4-氟苄基)哌啶盐酸盐 作用下， 以25的产率得到雷拉地尔
  参考文献：
  名称：

  European Journal of Medicinal Chemistry. 2011, 46, 2295-2309

  摘要：

  DOI：

文献信息

• Cyclic amine compounds as CCR5 antagonists
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06562978B1

  公开（公告）日：2003-05-13

  A compound of formula (I) (wherein R1 is a hydrogen atom, a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, R2 is a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, or R1 and R2 may combine to each other together with A to form a heterocyclic group which may be substituted; A is N or N+—R5.Y−(R5 is a hydrocarbon group; Y− is a counter anion); R3 is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; n is 0 or 1; R4 is a hydrogen atom, a hydrocarbon group which may be substituted, a heterocyclic group which may be substituted, an alkoxy group which may be substituted, an aryloxy group which may be substituted, or an amino group which may be substituted, E is a divalent aliphatic hydrocarbon group which may be substituted by group(s) other than oxo; G1 is a bond, CO or SO2; G2 is CO, SO2, NHCO, CONH or OCO; J is methine or a nitrogen atom; and each of Q and R is a bond or a divalent C1-3 aliphatic hydrocarbon which may be substituted; provided that J is methine when G2 is OCO, that one of Q and R is not a bond when the other is a bond and that each of Q and R is not substituted by oxo group(s) when G1 is a bond) or a salt thereof has a potent CCR5 antagonistic activity and can be advantageously used for the treatment or prevention of infectious disease of various HIV in human (e.g. AIDS).

  式（I）的化合物（其中R1是氢原子，可能被取代的碳氢基团，可能被取代的非芳香杂环基团，R2是可能被取代的碳氢基团，可能被取代的非芳香杂环基团，或R1和R2可以彼此结合与A一起形成可能被取代的杂环基团；A是N或N+—R5.Y−（R5是碳氢基团；Y−是一个对离子）；R3是可能被取代的环烃基团或可能被取代的杂环基团；n为0或1；R4是氢原子，可能被取代的碳氢基团，可能被取代的杂环基团，可能被取代的烷氧基团，可能被取代的芳基氧基团，或可能被取代的氨基团；E是可能被除氧以外的基团取代的二价脂肪族碳氢基团；G1是键，CO或SO2；G2是CO，SO2，NHCO，CONH或OCO；J是亚甲基或氮原子；Q和R中的每一个是键或可能被取代的二价C1-3脂肪族碳氢基团；条件是当G2为OCO时J为亚甲基，当另一个为键时Q和R中的一个不是键，当G1为键时Q和R中的每一个都不被氧基取代）或其盐具有强大的CCR5拮抗活性，并可优势用于治疗或预防人类体内各种HIV引起的传染病（例如艾滋病）。
• Chemical exploration of 4-(4-fluorobenzyl)piperidine fragment for the development of new tyrosinase inhibitors
  作者：Stefania Ferro、Laura De Luca、Maria Paola Germanò、Maria Rosa Buemi、Laura Ielo、Giovanna Certo、Margarita Kanteev、Ayelet Fishman、Antonio Rapisarda、Rosaria Gitto

  DOI：10.1016/j.ejmech.2016.10.030

  日期：2017.1

  demonstrated that several obtained compounds proved to be effective inhibitors showing IC50 values lower both than “lead compound” 1a and reference inhibitor kojic acid, as a well-known tyrosinase inhibitor. The inhibition kinetics analyzed by Lineweaver–Burk plots revealed that compounds 2 a-c and 10b act as non-competitive inhibitors while the most active inhibitor 2d (IC50 = 7.56 μM) is a mixed-type

  酪氨酸酶通过单酚羟基化为邻二酚而参与黑色素的产生。为了确定防止皮肤色素沉着和黑色素瘤的新疗法，对该酶的作用进行了广泛的研究。在这项工作中，我们最初确定了3-（4-苄基哌啶-1-基）-1-（1 H-吲哚-3-基）丙-1-酮（1a）是有希望的蘑菇酪氨酸酶抑制剂（IC 50  = 252μM）。 ）。然后，进行了几种化学修饰，并合成了与化合物1a相关的新类似物。生化分析表明，所获得的几种化合物被证明是有效的抑制剂，其IC 50值均低于“先导化合物” 1a和参考抑制剂曲酸，作为众所周知的酪氨酸酶抑制剂。通过Lineweaver-Burk图分析的抑制动力学表明，化合物2 ac和10b充当非竞争性抑制剂，而活性最高的抑制剂2d（IC 50  = 7.56μM）是混合型抑制剂。此外，进行了实验和计算结构研究，以阐明衍生物2d的结合模式。
• Piperidine derivatives as subtype selective N-methyl-D-aspartate antagonists
  申请人：——

  公开号：US20030018021A1

  公开（公告）日：2003-01-23

  Described are piperidines of Formula I 1 and pharmaceutically acceptable salts thereof. The compounds of Formula I are antagonists of NMDA receptor channel complexes useful for treating cerebral vascular disorders such as, for example, stroke, cerebral ischemia, central nervous system disorders, depression, trauma, hypoglycemia, neurodegenerative disorders, anxiety, migraine headache, convulsions, Parkinson's disease, aminoglycoside antibiotics-induced hearing loss, psychosis, glaucoma, CMV retinitis, opioid tolerance or withdrawal, pain, especially chronic pain, neuropathic pain, or surgical pain, or urinary incontinence.

  描述了式I的哌啶类化合物及其药用盐。式I的化合物是NMDA受体通道复合物的拮抗剂，可用于治疗脑血管疾病，如中风、脑缺血、中枢神经系统疾病、抑郁症、创伤、低血糖、神经退行性疾病、焦虑、偏头痛、抽搐、帕金森病、氨基糖苷类抗生素引起的听力损失、精神病、青光眼、巨细胞病毒性视网膜炎、阿片类耐受性或戒断症状、疼痛，尤其是慢性疼痛、神经病性疼痛或手术疼痛，以及尿失禁。
• [EN] DISUBTITUTED AZETIDINES, PYRROLIDINES, PIPERIDINES AND AZEPANES AS INHIBITORS OF MONOAMINE OXIDASE B FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] AZÉTIDINES, PYRROLIDINES, PIPÉRIDINES ET AZÉPANES DI-SUBSTITUÉS EN TANT QU'INHIBITEURS DE MONOAMINE OXYDASE B POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：UNIV OF LJUBLJANA

  公开号：WO2018055096A1

  公开（公告）日：2018-03-29

  This invention relates to new inhibitors of MAO-Bwith the general formula I, where substituents are described in patent description. Compounds can be in the form of pure enantiomers or as racemic mixtures, or in the form of pharmaceutically acceptable salts. The present invention relates to the use of these inhibitors for the alleviation of symptoms and treatment of acute and chronic neurological disorders, cognitive and neurodegenerative diseases.

  这项发明涉及具有一般式I的新MAO-B抑制剂，其中取代基在专利描述中有描述。化合物可以是纯对映体的形式，也可以是消旋混合物的形式，或者是药用盐的形式。本发明涉及利用这些抑制剂缓解症状和治疗急性和慢性神经疾病、认知和神经退行性疾病。
• SUBSTITUTED INDOLE/INDAZOLE-PYRIMIDINYL COMPOUNDS
  申请人：Selness Shaun R.

  公开号：US20120142696A1

  公开（公告）日：2012-06-07

  The present disclosure provides indole/indazole-pyrimidinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, having the structure of Formula (I): wherein W, X, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

  本公开提供了在治疗p38激酶介导的疾病（如淋巴瘤和自身免疫性疾病）中有用的吲哚/吲唑-嘧啶基化合物，其具有下式（I）的结构：其中W、X、R1、R2、R3、R4、R5和R6如详细描述中所定义；包含至少一种该化合物的药物组合物；以及使用该化合物治疗p38激酶介导疾病的方法。