1-(4-苯甲基哌啶-1-基)乙酮 | 101997-42-6

• 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: 1-(4-苯甲基哌啶-1-基)乙酮
• 英文名称: 1-(4-benzylpiperidin-1-yl)ethan-1-one
• 英文别名: 1-acetyl-4-benzylpiperidine；N-Acetyl-4-benzylpiperidine；1-(4-benzylpiperidin-1-yl)ethanone
• CAS: 101997-42-6
• 化学式: C₁₄H₁₉NO
• mdl: MFCD00495705
• 分子量: 217.311
• InChiKey: BKQOKWBHIBQLIH-UHFFFAOYSA-N

物化性质

• 沸点：
  362.8±11.0 °C(Predicted)
• 密度：
  1.049±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 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：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(4-苯甲基哌啶-1-基)乙酮 在 盐酸 、 氯磺酸 、 硫酸 、 potassium carbonate 、 锌 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 4-(4-methylsulfanylbenzyl)piperidine
  参考文献：
  名称：

  CCR5 antagonists as anti-HIV-1 agents. Part 3: Synthesis and biological evaluation of piperidine-4-carboxamide derivatives

  摘要：

  Replacement of the 5-oxopyrrolidin-3-yl fragment in the previously reported lead structure with a 1-acetylpiperidin-4-yl group led to the discovery of a novel series of potent CCR5 antagonists. Introduction of small hydrophobic substituents on the central phenyl ring increased the binding affinity, providing low to sub-nanomolar CCR5 antagonists. The selected compound 11f showed excellent antiviral activity against CCR5-using HIV-1 replication in human peripheral blood mononuclear cells (EC50 = 0.59 nM) and an acceptable pharmacokinetic profile in dogs. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.10.013
• 作为产物：
  描述：

  4-苄基哌啶 、 乙酸酐 反应 1.0h， 以100%的产率得到1-(4-苯甲基哌啶-1-基)乙酮
  参考文献：
  名称：

  CCR5 antagonists as anti-HIV-1 agents. Part 2: Synthesis and biological evaluation of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N′-diphenylureas

  摘要：

  We have previously reported the novel lead compound 1a as a CCR5 antagonist for treatment of HIV-1 infection. SAR studies on incorporating various acyl groups as a replacement for the 5-oxopyrrolidine-3-carbonyl group of the lead structure resulted in the discovery of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N-1-diphenylurea (4a) with significantly improved CCR5 binding affinity. Substitutions (4-Cl, 4e,f; 4-Me, 4i) on the N'-phenyl ring further increased the binding affinity. Introduction of polar substituents on the phenyl ring of the 4-benzylpiperidine moiety enhanced the inhibitory activity of the HIV-1 envelope-mediated membrane fusion (4v,w), suggesting that polar substituents at this position can interfere effectively with HIV-1 cell entry. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.004

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）。
• Secondary Amides of (<i>R</i>)-3,3,3-Trifluoro-2-hydroxy-2-methylpropionic Acid as Inhibitors of Pyruvate Dehydrogenase Kinase
  作者：Thomas D. Aicher、Robert C. Anderson、Jiaping Gao、Suraj S. Shetty、Gary M. Coppola、James L. Stanton、Douglas C. Knorr、Donald M. Sperbeck、Leonard J. Brand、Christine C. Vinluan、Emma L. Kaplan、Carol J. Dragland、Hollis C. Tomaselli、Amin Islam、Robert J. Lozito、Xilin Liu、Wieslawa M. Maniara、William S. Fillers、Dominick DelGrande、R. Eric Walter、William R. Mann

  DOI：10.1021/jm990358+

  日期：2000.1.1

  6-tetrahydropyridine)thiourea, SDZ048-619 (1), is a modest inhibitor (IC(50) = 180 microM) of pyruvate dehydrogenase kinase (PDHK). In an optimization of the N-methylcarbothioamide moiety of 1, it was discovered that amides with a small acyl group, in particular appropriately substituted amides of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid, are inhibitors of PDHK. Utilizing this acyl moiety, herein is

  N'-甲基-N-（4-叔丁基-1,2,5,6-四氢吡啶）硫脲SDZ048-619（1）是丙酮酸脱氢酶激酶的适度抑制剂（IC（50）= 180 microM） （PDHK）。在最优化1的N-甲基碳硫酰胺部分时，发现具有小的酰基的酰胺，特别是（R）-3,3,3-三氟-2-羟基-2-甲基-2-丙酸的适当取代的酰胺，是PDHK的抑制剂。本文报道了利用该酰基部分的原理，其导致一系列酰化哌嗪衍生物的优化。哌嗪在2和5位上的甲基取代（具有S和R绝对立体化学）显着提高了前导化合物的效价（> 1,000倍）。当哌嗪的4位被电子贫乏的苯甲酰基部分取代时，该系列化合物的口服生物利用度良好且最佳（通过AUC测定）。（+）-1-N- [2,5-（S，R）-二甲基-4-N-（4-氰基苯甲酰基）哌嗪]-（R）-3,3，3-三氟-2-羟基-2 -甲基丙酰胺（14e）抑制PDHK在主要酶促测定中的IC（50）为16 +/-
• [EN] CYCLIC AMINE COMPOUNDS AS CCR5 ANTAGONISTS<br/>[FR] COMPOSES D'AMINE CYCLIQUE UTILISES COMME ANTAGONISTES DE CCR5
  申请人：TAKEDA CHEMICAL INDUSTRIES LTD

  公开号：WO2001025200A1

  公开（公告）日：2001-04-12

  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 R?1 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 SO¿2; G?2 is CO, SO¿2?, 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 G?1¿ 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).

  化合物式为（I）（其中R1是氢原子，可被取代的碳氢基团，可被取代的非芳香杂环基团，R2是可被取代的碳氢基团，可被取代的非芳香杂环基团，或R1和R2可以与A一起结合形成可被取代的杂环基团；A是N或N+ -R5 • Y-（R5是碳氢基团；Y-是反离子）；R3是可被取代的环烃基团或可被取代的杂环基团；n为0或1；R4是氢原子，可被取代的碳氢基团，可被取代的杂环基团，可被取代的烷氧基，可被取代的芳氧基，或可被取代的氨基，E是可被除氧基以外的基取代的二价脂肪烃基团；G1是键，CO或SO2；G2是CO，SO2，NHCO，CONH或OCO；J是甲基或氮原子；Q和R中的每一个都是一个键或一个可被取代的二价C1-3脂肪基团；前提是当G2是OCO时，J是甲基，当另一个是键时，其中一个不是键，当G1是键时，Q和R中的每一个都没有被氧基团取代）或其盐具有强效的CCR5拮抗活性，并可用于人类各种HIV感染疾病（例如艾滋病）的治疗或预防。
• Use of compounds having ccr antagonism
  申请人：Tsuchimori Noboru

  公开号：US20050245537A1

  公开（公告）日：2005-11-03

  It is intended to provide preventives/remedies for graft-versus-host disease and/or rejection in organ or bone marrow transplantation, rheumatoid arthritis, autoimmune diseases, allergic diseases, ischemic cerebral cell injury, myocardial infarction, chronic nephritis and arteriosclerosis. The above object can be achieved by preventives/remedies for graft-versus-host disease and/or rejection in organ or bone marrow transplantation, rheumatoid arthritis, autoimmune diseases, allergic diseases, ischemic cerebral cell injury, myocardial infarction, chronic nephritis and arteriosclerosis characterized by containing a specific compound having a CCR (CC chemokine receptor) antagonism.

  本发明旨在为移植手术中的移植物抗宿主病和/或排斥反应、类风湿性关节炎、自身免疫疾病、过敏性疾病、缺血性脑细胞损伤、心肌梗死、慢性肾炎和动脉硬化提供预防和治疗措施。上述目标可以通过包含具有CCR（CC趋化因子受体）拮抗作用的特定化合物的移植物抗宿主病和/或排斥反应、类风湿性关节炎、自身免疫疾病、过敏性疾病、缺血性脑细胞损伤、心肌梗死、慢性肾炎和动脉硬化的预防和治疗措施来实现。
• Urea compounds, process for producing the same and use thereof
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06787650B1

  公开（公告）日：2004-09-07

  A compound of the formula: [wherein R1 is a hydrocarbon group which may be substituted; R2 is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; R3 is halogen atoms, a carbamoyl group which may be substituted, a sulfamoyl group which may be substituted, an acyl group derived from sulfonic acid, a C1-4 alkyl group which may be substituted, a C1-4 alkoxy group which may be substituted, an amino group which may be substituted, a nitro group or a cyano group; R4 is hydrogen atoms or a hydroxy group; n is 0 or 1; and p is 0 or 1 to 4]; or a salt thereof, has potent CCR5 antagonistic activity and can be advantageously used as a medicament for inhibition of HIV infection to human peripheral blood mononuclear cells, especially for the treatment or prevention of AIDS.

  该化合物的化学式为：[其中R1是一个可以被取代的碳氢基团；R2是一个可以被取代的环状碳氢基团或杂环基团；R3是卤素原子、可以被取代的氨基甲酰基、可以被取代的磺酰胺基、由磺酸衍生的酰基、可以被取代的C1-4烷基、可以被取代的C1-4烷氧基、可以被取代的氨基、硝基或氰基；R4是氢原子或羟基；n为0或1；p为0或1至4];或其盐，具有强效的CCR5拮抗活性，并可优势地用作药物，以抑制HIV感染人类外周血单个核细胞，特别是用于治疗或预防艾滋病。