1-benzyl-N-(3,4-dichlorophenyl)piperidin-4-amine | 115661-42-2

• 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: 1-benzyl-N-(3,4-dichlorophenyl)piperidin-4-amine
• 英文别名: 1-Benzyl-4-[(3,4-dichlorophenyl)amino]piperidine
• CAS: 115661-42-2
• 化学式: C₁₈H₂₀Cl₂N₂
• 分子量: 335.276
• InChiKey: HZCYTQCPVNIIKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-benzyl-N-(3,4-dichlorophenyl)piperidin-4-amine 在 甲醇 、 1-氯乙基氯甲酸酯 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 1-{2-[4-(N-methoxyacetyl-(3,4-dichlorophenyl)amino)piperidino]ethyl}-3-isopropenyl-2(3H)-benzimidazolone
  参考文献：
  名称：

  Pharmacological profile of a novel series of NK1 antagonists. In vitro and in vivo potency of benzimidazolone derivatives

  摘要：

  By low throughput examination of our chemical library, compound 7 was selected as a lead NK, antagonist with a K-i of 7.1 nM. Modifications of its structure led to the finding that the in vitro potency could be markedly enhanced by disubstituting the anilino phenyl ring as in compounds 13 or 22. Human binding data correlated rather well with results obtained with in vitro animal mice; compound 13 was the most active with ED50 of 0.001 and 0.3 mg/kg after iv and po administration respectively. Furthermore, antagonist 71 was found to be a potent inhibitor of SP-induced bronchoconstriction in guinea-pigs with an ED50 between 0.1 and 0.03 mg/kg iv. Furthermore, upon oral administration, 71 was observed to be active in a model of SP-induced bronchial hypersensitivity in mice, with an ID50 of around 3 mg/kg.

  DOI：

  10.1016/s0223-5234(97)82771-7
• 作为产物：
  描述：

  (1-Benzyl-piperidin-4-ylidene)-(3,4-dichloro-phenyl)-amine 在 sodium tetrahydroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 1-benzyl-N-(3,4-dichlorophenyl)piperidin-4-amine
  参考文献：
  名称：

  A new series of M3 muscarinic antagonists based on the 4-amino-piperidine scaffold

  摘要：

  A series of 4-amino-piperidine containing molecules have been synthesized and structure-affinity relationship toward the M3-muscarinic receptor has been investigated. Chemical modulations provided molecules with K-i for the human M3-R up to 1 nM with variable selectivity (3- to 40-fold) over the human M2-R. Compounds 2 (pA(2) = 8.3, 8.6) demonstrates in vitro on guinea pig bladder and ileal strips potent anticholinergic properties and tissue selectivity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00487-0

文献信息

• C-terminal modified Enkephalin-like tetrapeptides with enhanced affinities at the kappa opioid receptor and monoamine transporters
  作者：Mehr-un-Nisa、Munawar A. Munawar、David Rankin、Victor J. Hruby、Frank Porreca、Yeon Sun Lee

  DOI：10.1016/j.bmc.2021.116509

  日期：2021.12

  positions 1 and 4 were substituted by Dmt and Phe(p-X) residues, respectively, showed the excellent binding affinities at three opioid receptors. Among them, Dmt-D-Tic-Gly-Phe(4-F)-DPP was the most promising considering its excellent opioid affinities, particularly unexpected high binding affinity (Ki = 0.13 nM) at the KOR, and moderate interactions with serotonin/norepinephrine reuptake inhibitors (SNRIs)

  设计、合成了一系列新的脑啡肽样四肽类似物，其C末端被N -(3,4-二氯苯基)- N -(哌啶-4-基)丙酰胺 (DPP) 部分修饰，并对其进行了测试阿片受体和单胺转运蛋白的结合亲和力，以评估它们治疗慢性疼痛的潜在多功能活性。大多数配体在阿片受体上表现出纳摩尔范围内的高结合亲和力，对 mu-阿片受体 (MOR) 和 kappa-阿片受体 (KOR) 具有轻微的 delta-阿片受体 (DOR) 选择性，并且在微摩尔范围内表现出低结合亲和力单胺转运蛋白、SERT 和 NET。1位和4位被Dmt和Phe( p-X) 残基分别对三种阿片受体表现出极好的结合亲和力。其中，Dmt - D -Tic-Gly-Phe(4-F)-DPP 是最有前途的，因为它具有出色的阿片类药物亲和力，尤其是在 KOR 处出乎意料的高结合亲和力 ( Ki = 0.13 nM)，以及与血清素的适度相互作用/去甲肾上腺素再摄取抑制剂
• [EN] N-ARYL-N-PIPERIDIN-4-YL-PROPIONAMIDE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS<br/>[FR] DÉRIVÉS DE N-ARYL-N-PIPÉRIDIN-4-YL-PROPIONAMIDE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA RÉABSORPTION DES NEUROTRANSMETTEURS MONOAMINES
  申请人：NEUROSEARCH AS

  公开号：WO2009077585A1

  公开（公告）日：2009-06-25

  This invention relates to /\/-aryl-/\/-piperidin-4-yl-propionannide derivatives for use as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy, such as for the treatment of pain, and to pharmaceutical compositions comprising the compounds, and to novel compounds.

  这项发明涉及用作单胺神经递质再摄取抑制剂的/\/-芳基-/\/-哌啶-4-基-丙酰胺衍生物。在其他方面，该发明涉及这些化合物在治疗方法中的应用，例如用于治疗疼痛，并且涉及包含这些化合物的药物组合物，以及新化合物。
• Piperidine compounds
  申请人：Adir et Compagnie

  公开号：US05652246A1

  公开（公告）日：1997-07-29

  The invention relates to the compounds of formula (I): ##STR1## in which: R.sub.1 represents alkyl, phenyl, naphthyl, pyridyl or thienyl group, each phenyl, naphthyl, pyridyl or thienyl optionally being substituted, R.sub.2 represents a hydrogen atom or a substituted or unsubstituted alkyl, substituted or unsubstituted phenyl, cycloalkyl, piperidino or substituted or unsubstituted amino group, X represents CO or SO.sub.2, R.sub.3 represents hydrogen or alkyl, R.sub.4 represents alkyl, substituted or unsubstituted phenyl or trihalomethyl, or else R.sub.3 and R.sub.4 form, together with the carbon atoms which carry them, cyclo(C.sub.3 -C.sub.7)alkenyl, A represents phenyl, naphthyl or pyridyl ring, each phenyl, naphthyl or pyridyl ring optionally being substituted, their isomers, the corresponding quaternary ammonium salts of the piperidine and their addition salts with a pharmaceutically acceptable acid, an medicinal products containing the same are useful as antagonists of NK.sub.1 receptors.

  该发明涉及以下公式（I）的化合物：##STR1## 在其中：R.sub.1代表烷基，苯基，萘基，吡啶基或噻吩基，每个苯基，萘基，吡啶基或噻吩基可选择地被取代，R.sub.2代表氢原子或取代或未取代的烷基，取代或未取代的苯基，环烷基，哌啶基或取代或未取代的氨基，X代表CO或SO.sub.2，R.sub.3代表氢或烷基，R.sub.4代表烷基，取代或未取代的苯基或三卤甲基，否则R.sub.3和R.sub.4与携带它们的碳原子一起形成环（C.sub.3 -C.sub.7）烯基，A代表苯基，萘基或吡啶环，每个苯基，萘基或吡啶环可选择地被取代，它们的异构体，哌啶的相应季铵盐及其与药学上可接受的酸形成的加合盐，含有它们的药物制剂作为NK.sub.1受体的拮抗剂是有用的。
• [EN] N-ARYL-N-PIPERIDIN-4-YL-PROPIONAMIDE DERIVATIVES AND THEIR USE AS OPIOID RECEPTOR LIGANDS<br/>[FR] DÉRIVÉS DE N-ARYL-N-PIPÉRIDIN-4-YLPROPIONAMIDE ET LEUR UTILISATION COMME LIGANDS DES RÉCEPTEURS OPIOÏDES
  申请人：NEUROSEARCH AS

  公开号：WO2009077584A1

  公开（公告）日：2009-06-25

  This invention relates to novel N-aryl -N-piperidin-4 -yl -propionamide derivatives (I) useful as opioid receptor ligands. In other aspects the invention relates to the use of these compounds in a method for therapy, such as for the treatment of pain, and to pharmaceutical compositions comprising the compounds of the invention.

  该发明涉及一种新型N-芳基-N-哌啶-4-基-丙酰胺衍生物（I），可用作阿片受体配体。在其他方面，该发明涉及将这些化合物用于治疗方法，例如用于治疗疼痛，以及包含该发明化合物的药物组合物。
• [EN] N-ARYL-N-PIPERIDIN-4-YL-PROPIONAMIDE DERIVATIVES AND THEIR USE AS OPIOID RECEPTOR LIGANDS<br/>[FR] DÉRIVÉS DE N-ARYL-N-PIPÉRIDIN-4-YL-PROPIONAMIDE ET LEUR UTILISATION COMME LIGANDS DES RÉCEPTEURS AUX OPIOÏDES
  申请人：NEUROSEARCH AS

  公开号：WO2009077574A1

  公开（公告）日：2009-06-25

  This invention relates to novel /\/-aryl-/\/-piperidin-4-yl-propionamide derivatives useful as opioid receptor ligands. In other aspects the invention relates to the use of these compounds in a method for therapy, such as for the treatment of pain, and to pharmaceutical compositions comprising the compounds of the invention.

  这项发明涉及新颖的/\/-芳基-/\/-哌啶-4-基-丙酰胺衍生物，可用作阿片受体配体。在其他方面，该发明涉及将这些化合物用于治疗方法，例如用于治疗疼痛，并且涉及包含该发明化合物的药物组合物。