2-chloro-1-(4-(4-chlorobenzyl)piperazin-1-yl)ethanone | 123580-74-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-chloro-1-(4-(4-chlorobenzyl)piperazin-1-yl)ethanone
• 英文别名: 1-Chloroacetyl-4-(4-chorobenzyl)-piperazine；2-Chloro-1-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]ethanone
• CAS: 123580-74-5
• 化学式: C₁₃H₁₆Cl₂N₂O
• 分子量: 287.189
• InChiKey: AJZZGIDTBJLUTQ-UHFFFAOYSA-N

物化性质

• 沸点：
  412.3±45.0 °C(Predicted)
• 密度：
  1.296±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-1-(4-(4-chlorobenzyl)piperazin-1-yl)ethanone 在 硫酸 、 sodium ethanolate 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 72.0h， 生成 6-amino-5-[4-(4-chlorobenzyl)piperazine-1-carbonyl]-2,3-dihydro-1H-pyrrolizine-7-carboxamide
  参考文献：
  名称：

  设计，合成，体外和体内评估新型以吡咯烷嗪为基础的化合物，这些化合物具有潜在的胆碱酯酶抑制剂和抗阿尔茨海默氏病活性。

  摘要：

  设计，合成和评估了一系列新型的基于吡咯嗪的化合物（4 – 6和9 – 11）作为潜在的抗阿尔茨海默病药物。大多数测试化合物对h AChE的选择性均超过h BChE，并在体外有效抑制了自我诱导的淀粉样β聚集。在这些衍生物中，化合物10显示高选择性朝ħ乙酰胆碱酯酶（KI = 1.47±0.63μM为ħ的AChE和Ki = 40.15±3.31μM为ħ的BChE）。但是，化合物11对h AChE和h均显示双重抑制作用BChE在亚微摩尔范围内（Ki分别为0.40±0.03和0.129±0.009μM）。新配体的动力学研究表明，h AChE和h BChE均具有竞争性抑制类型。此外，化合物10和11对多奈哌齐对人神经母细胞瘤（SH-SY5Y）和正常人肝细胞（THLE2）的细胞毒性较低或相当。体内研究证实，这两种化合物均能够改善东-碱诱导的AD小鼠的认知功能障碍。最后，在h AChE活性位点对化合物10

  DOI：

  10.1016/j.bioorg.2019.103312
• 作为产物：
  描述：

  4-氯氯苄 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-chloro-1-(4-(4-chlorobenzyl)piperazin-1-yl)ethanone
  参考文献：
  名称：

  Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors

  摘要：

  Based on the literature-reported compensatory effect of PI3K on Abl inhibition and the improved preclinical effect of drug combination of Abl and PI3K inhibitors, a series of compounds bearing novel scaffold of (S)-3-aminopyrrolidine was identified as Abl and PI3K dual inhibitors through support vector machine screening tool, which were subsequently synthesized and tested. Most compounds demonstrated promising cytoxicity against a CML leukemia cell-line K562 and moderate inhibition against Abl and PI3K kinases. These compounds induced no apoptosis in K562 cell-line, suggesting that their cytotoxic activities are unlikely duo to other known anti-CML mechanisms. Molecular docking study further showed that the compound 5k could bind with both Abl and PI3K, but the weaker binding with Abl compared to Imatinib is consistent with its low kinase inhibitory rates. These plus literature-reported evidences suggest that the promising cytotoxic effect of our novel compounds might be due to the collective effect of Abl and PI3K inhibition. (c) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.020

文献信息

• Indoline and piperazine containing derivatives as a novel class of mixed D2/D4 receptor antagonists. Part 1: Identification and structure–activity relationships
  作者：He Zhao、Andrew Thurkauf、Xiaoshu He、Kevin Hodgetts、Xiaoyan Zhang、Stanislaw Rachwal、Renata X. Kover、Alan Hutchison、John Peterson、Andrzej Kieltyka、Robbin Brodbeck、Renee Primus、Jan W.F. Wasley

  DOI：10.1016/s0960-894x(02)00655-8

  日期：2002.11

  Optimization of the lead compound 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,3-dihydro-indol-1-yl)-ethanone 1 by systematic structure-activity relation (SAR) studies lead to two potent compounds 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone 2n and 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone 7b. Their related synthesis was

  通过系统结构-活性关系最优化铅化合物2-[-4-（4-氯苄基）-哌嗪-1-基] -1-（2,3-二氢-吲哚-1-基）-乙酮1 （SAR）研究产生了两种有效的化合物2-[-4-（4-氯-苄基）-哌嗪-1-基] -1-（2-甲基-2,3-二氢-吲哚-1-基）-乙酮2n和2-[-4-（4-氯苄基）-哌嗪-1-基] -1-（2-甲基-2,3-二氢-吲哚-1-基）-乙酮7b。还报道了它们的相关合成。
• [EN] PYRIDAZINONE DERIVATIVES WITH PHARMACEUTICAL ACTIVITY<br/>[FR] DERIVES DE PYRIDAZINONE A ACTIVITE PHARMACEUTIQUE
  申请人：NISSAN CHEMICAL INDUSTRIES LTD.

  公开号：WO1995001343A1

  公开（公告）日：1995-01-12

  (EN) A 3(2H)-pyridazinone derivative of formula (I), its salt, a process for its production and a pharmaceutical composition containing it, wherein each of R1, R2 and R3 which are independent of one another, is a hydrogen atom or a C1-4 alkyl group, X is a chlorine atom or a bromine atom, Y1 is a hydrogen atom, a halogen atom, a nitro group, an amino group or a C1-4 alkoxy group, Y2 is a hydrogen atom, a halogen atom, a hydroxyl group, a C1-4 alkyl group or a C1-4 alkoxy group, A is a C1-5 alkylene chain which may be substituted by a hydroxyl group, B is a carbonyl group or a methylene chain which may be substitued by a C1-4 alkyl group, and each of R4 and R5 which are independent of each other, is a C1-4 alkyl group, or R4 is a hydrogen atom and R5 is -Z-Ar (wherein Z is a C1-5 alkylene chain, and Ar is an aromatic 6-membered ring which may contain a nitrogen atom), or R4 and R5 together form a C2-6 cyclic alkylene group, or R4 and R5 form together with the adjacent nitrogen atom a 4-substituted piperazine ring of formula (a), wherein R6 is a C1-4 alkyl group.(FR) Dérivé de 3(2H)-pyridazinone répondant à la formule (I), son sel, son procédé de production et composition pharmaceutique le contenant. Dans ladite formule, R1, R2 et R3, indépendamment les uns des autres, représentent un atome d'hydrogène ou un groupe alkyle C1-4; X représente un atome de chlore ou de brome; Y1 représente un atome d'hydrogène, un atome d'halogène, un groupe nitro, un groupe amino ou un groupe alcoxy C1-4; Y2 représente un atome d'hydrogène, un atome d'halogène, un groupe hydroxyle, un groupe alkyle C1-4 ou un groupe alcoxy C1-4; A représente une chaîne alkylène C1-5 éventuellement substituée par un groupe hydroxyle; B représente un groupe carbonyle ou une chaîne méthylène éventuellement substituée par un groupe alkyle C1-4; et R4 et R5, indépendamment l'un de l'autre, représentent un groupe alkyle C1-4, ou R4 représente un atome d'hydrogène et R5 représente -Z-Ar (où Z représente une chaîne alkylène C1-5 et Ar représente un cycle aromatique à 6 chaînons pouvant contenir un atome d'azote), ou R4 et R5, pris ensemble, forment un groupe alkylène cyclique C2-6, ou bien R4 et R5, pris ensemble, forment avec l'atome d'azote voisin un cycle pipérazine substitué en position 4 et répondant à la formule (a), dans laquelle R6 représente un groupe alkyle C1-4.

  一种3（2H）-吡啶嗪酮衍生物，其化学式为（I），其盐，其生产过程以及含有它的药物组合物。其中，R1、R2和R3分别独立地表示氢原子或C1-4烷基，X表示氯原子或溴原子，Y1表示氢原子、卤素原子、硝基、氨基或C1-4烷氧基，Y2表示氢原子、卤素原子、羟基、C1-4烷基或C1-4烷氧基，A表示可被羟基替代的C1-5烷基链，B表示可被C1-4烷基替代的羰基或亚甲基链，R4和R5分别独立地表示C1-4烷基，或者R4表示氢原子，R5表示-Z-Ar（其中Z表示C1-5烷基链，Ar表示可能含有氮原子的芳香6元环），或者R4和R5一起形成C2-6环烷基链，或者R4和R5与相邻氮原子一起形成化学式（a）的4-取代哌嗪环，其中R6表示C1-4烷基。
• Synthesis, and docking studies of novel tetrazole-S-alkyl derivatives as antimicrobial agents
  作者：Ulviye Acar Çevik、Ismail Celik、Ayşen Işık、Ülküye Dudu Gül、Gizem Bayazıt、Hayrani Eren Bostancı、Yusuf Özkay、Zafer Asım Kaplancıklı

  DOI：10.1080/10426507.2022.2117812

  日期：2023.2.1

  drug, with a MIC value of 7.81 µg/mL. All the derivatives were efficiently synthesized by a two-step process. The structure of the newly synthesized compounds was elucidated by their 1H NMR, 13C NMR, LC-MS/MS, and elemental analysis. In this study, the detailed synthesis, spectroscopic and biological evaluation data are reported. Molecular docking studies of all compounds were performed with the sterol

  摘要 合成了一系列新型四唑-S-烷基-哌嗪衍生物，并评估了它们对白色念珠菌(ATCC 24433)、克柔念珠菌(ATCC 6258) 和近光滑念珠菌(ATCC 22019) 的抗真菌活性以及对大肠杆菌的抗菌活性。大肠杆菌(ATCC 25922)、粘质链球菌 ( ATCC 8100)、肺炎克雷伯菌(ATCC 13883)、铜绿假单胞菌(ATCC 27853)、粪肠球菌(ATCC 2942)、枯草杆菌(ATCC)、金黄色葡萄球菌(ATCC ) 29213)、表皮葡萄球菌(ATCC 12228)。在合成的化合物中，1-(4-环己基哌嗪-1-基)-2-((1-甲基-1 H-tetrazol-5-yl)thio)ethan-1-one ( 2b ) (MIC = 7.81 µg/mL) 和 1-(4-(4-chlorobenzyl)piperazin-1-yl)-2-((1-methyl -1 H
• Piperazine derivatives and their use as anti-inflammatory agents
  申请人：Schering Aktiengesellschaft

  公开号：EP1254899B1

  公开（公告）日：2005-05-25
• Structure–activity relationships of novel, highly potent, selective, and orally active CCR1 antagonists
  作者：Yun Feng Xie、Kirk Lake、Kathleen Ligsay、Mallareddy Komandla、Ila Sircar、Gobi Nagarajan、Jian Li、Kui Xu、Jason Parise、Lisa Schneider、Ding Huang、Juping Liu、Kevin Dines、Naoki Sakurai、Miguel Barbosa、Rick Jack

  DOI：10.1016/j.bmcl.2007.03.104

  日期：2007.6

  Design and synthesis of a series of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl)-2-oxoethoxy)phenylamino)cyclobutenedione derivatives as novel CCRI antagonists are described. Structure-activity relationship studies led to the identification of compound 22, which demonstrated potent binding activity, functional antagonism of CCR1 as well as good species cross-reactivity. In addition, compound 22 also showed desirable pharmacokinetic profiles and was selected for in vivo studies in the mouse collagen-induced arthritis model. (c) 2007 Elsevier Ltd. All rights reserved.