1-(2-氯苄基)-4-哌啶胺 | 92539-15-6

• 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-(2-氯苄基)-4-哌啶胺
• 英文名称: 1-(o-chlorobenzyl)-4-aminopiperidine
• 英文别名: 1-(2-chlorobenzyl)piperidin4-amine；1-(o-Chlorbenzyl)-4-aminopiperidin；4-amino-1-(2-chlorophenyl)methyl piperidine；4-amino-1-(2-chlorobenzyl)piperidine；1-(2-chloro-benzyl)-piperidin-4-ylamine；1-(2-Chlorobenzyl)piperidin-4-amine；1-[(2-chlorophenyl)methyl]piperidin-4-amine
• CAS: 92539-15-6
• 化学式: C₁₂H₁₇ClN₂
• 分子量: 224.733
• InChiKey: DAGOWXSFYONSNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 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：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  1-(2-氯苄基)-4-哌啶胺 在 铁粉 、 potassium carbonate 、 氯化铵 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 4-chloro-1-(1-(2-chlorobenzyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one
  参考文献：
  名称：

  Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias

  摘要：

  While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal beta arrestin-mediated signaling because MOR agonist-treated beta arrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimization of piperidine benzimidazolone MOR agonists that together display a wide range of bias (G/beta arr2). We identify structural features affecting potency and maximizing bias and show that many compounds have desirable properties, such as long half-lives and high brain penetration.

  DOI：

  10.1021/acs.jmedchem.8b01136
• 作为产物：
  描述：

  哌啶-4-甲酰胺 在 caesium carbonate 、 [双(三氟乙酰氧基)碘]苯 、 potassium iodide 作用下， 以 水 、 3-戊酮 、 乙腈 为溶剂， 反应 5.0h， 生成 1-(2-氯苄基)-4-哌啶胺
  参考文献：
  名称：

  Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias

  摘要：

  While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal beta arrestin-mediated signaling because MOR agonist-treated beta arrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimization of piperidine benzimidazolone MOR agonists that together display a wide range of bias (G/beta arr2). We identify structural features affecting potency and maximizing bias and show that many compounds have desirable properties, such as long half-lives and high brain penetration.

  DOI：

  10.1021/acs.jmedchem.8b01136

文献信息

• [EN] METHODS AND COMPOSITIONS OF INHIBITING DCN1-UBC12 INTERACTION<br/>[FR] PROCÉDÉS ET COMPOSITIONS D'INHIBITION DE L'INTERACTION DCN1-UBC12
  申请人：ST JUDE CHILDREN'S RES HOSPITAL

  公开号：WO2017049295A1

  公开（公告）日：2017-03-23

  In one aspect, the invention relates to substituted l-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1 -mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，本发明涉及替代的l-苯基-3-(哌啶-4-基)脲类似物，其衍生物和相关化合物，这些化合物可用作DCN1-UBC12相互作用抑制剂和DCN1介导的卡林-环形酶活性抑制剂，制备方法，包含这些化合物的药物组合物，使用所披露的化合物和组合物治疗疾病的方法，治疗与DCN1-UBC12相互作用功能障碍相关的疾病的方法，治疗与DCN1介导的卡林-环形酶活性功能障碍相关的疾病的方法，包含所披露的化合物和组合物的男性避孕方法，以及包含所披露的化合物和组合物的试剂盒。本摘要旨在作为在特定领域进行搜索的扫描工具，并不打算限制本发明。
• Discovery of a potent histone deacetylase (HDAC) 3/6 selective dual inhibitor
  作者：Uttara Soumyanarayanan、Pondy Murugappan Ramanujulu、Nurulhuda Mustafa、Shozeb Haider、Adina Huey Fang Nee、Jie Xin Tong、Kevin S.W. Tan、Wee Joo Chng、Brian W. Dymock

  DOI：10.1016/j.ejmech.2019.111755

  日期：2019.12

  Herein, we report the discovery of a dual histone deacetylase inhibitor displaying a unique HDAC3/6 selectivity profile. An initial strategy to merge two epigenetic pharmacophores resulted in the discovery of potent HDAC6 inhibitors with selectivity over HDAC1. Screening in an HDAC panel revealed additional low nanomolar inhibition only against HDAC3. Low micromolar antiproliferative activities against

  在本文中，我们报告发现了一种双组蛋白脱乙酰基酶抑制剂，该抑制剂显示出独特的HDAC3 / 6选择性特征。合并两个表观遗传药效团的初始策略导致发现了对HDAC1具有选择性的强效HDAC6抑制剂。在HDAC面板中进行的筛选显示，仅对HDAC3具有较低的纳摩尔抑制作用。对一种优选分子24c的药效学研究支持了对两种乳腺癌和四种血液学癌细胞系的低微摩尔抗增殖活性，证实了细胞中HDAC的抑制作用。凋亡被确定为主要的细胞死亡途径之一。针对HDAC1、2、3和6的24c建模研究进一步提供了与化合物效价相关的特定残基定向的见解，从而解释了所观察到的HDAC3 / 6选择性。该化合物的一部分也表现出良好的抗疟活性，特别是对恶性疟原虫的耐氯喹菌株K1。体外研究表明，良好的DMPK谱值得进一步研究这些化合物的治疗潜力。
• Rational Design and Multibiological Profiling of Novel Donepezil–Trolox Hybrids against Alzheimer’s Disease, with Cholinergic, Antioxidant, Neuroprotective, and Cognition Enhancing Properties
  作者：Pei Cai、Si-Qiang Fang、Xue-Lian Yang、Jia-Jia Wu、Qiao-Hong Liu、Hao Hong、Xiao-Bing Wang、Ling-Yi Kong

  DOI：10.1021/acschemneuro.7b00257

  日期：2017.11.15

  A novel series of donepezil-trolox hybrids were designed, synthesized, and evaluated as multifunctional ligands against Alzheimer’s disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions

  设计，合成和评估了一系列新的多奈哌齐-trolox杂种，作为对抗阿尔茨海默氏病（AD）的多功能配体。生物学测定表明，这些衍生物对乙酰胆碱酯酶（AChE）和单胺氧化酶B（MAO-B）具有中等至良好的抑制活性，并具有显着的抗氧化作用。最佳化合物6d表现出平衡的功能，对h AChE（IC 50 = 0.54μM）和h MAO-B（IC 50 = 4.3μM）具有良好的抑制作用，具有显着的抗氧化活性（通过DPPH方法测得的IC 50为41.33μMIC 50、1.72和1.79 trolox当量通过ABTS和ORAC方法），优异的铜螯合和Aβ1–42聚集抑制作用。此外，细胞测试表明6d具有极低的毒性，并且能够抵抗氧化毒素（H 2 O 2，鱼藤酮和寡霉素-A）引起的神经毒性。最重要的是，在小鼠模型中口服6d表现出对东pol碱引起的急性记忆缺陷以及d-半乳糖（d -gal）和AlCl 3引起的慢性氧化
• Claulansine F–Donepezil Hybrids as Anti-Alzheimer’s Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities
  作者：Yingda Zang、Ke Liu、Weiping Wang、Chuangjun Li、Jie Ma、Jingzhi Yang、Xinyi Chen、Xiaoliang Wang、Dongming Zhang

  DOI：10.3390/molecules26051303

  日期：——

  The multifactorial nature of Alzheimer’s disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F–donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC50) 1.63–4.62 μM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen–glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood–brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation.

  阿尔茨海默病（AD）的多因素性质需要开发多靶点药物，以应对关键的病理过程。总共设计和合成了26种Claulansine F-donepezil杂合物作为多靶点药物。在这些化合物中，有六种表现出优秀的乙酰胆碱酯酶（AChE）抑制活性（半最大抑制浓度（IC50）为1.63-4.62μM）。此外，（E）-3-（8-（叔丁基）-3,3-二甲基-3,11-二氢吡喃[3,2-a]咔唑-5-基）-N-（（1-（2-氯苯甲基）哌啶-4-基）甲基）丙烯酰胺（6bd）对OGD/R（氧-葡萄糖剥夺/再氧化）表现出比Claulansine F更好的神经保护作用。此外，6bd在体外可以穿越血脑屏障。更重要的是，与雷达伏酮相比，6bd具有更强的自由基清除活性。分子对接研究揭示了6bd可以与AChE的催化活性位点相互作用。所有这些出色的体外结果表明6bd作为一个值得进一步研究的领先结构。
• Antihypertensive isoindole derivatives
  申请人：Mead Johnson & Company

  公开号：US04495194A1

  公开（公告）日：1985-01-22

  Novel phthalimide intermediates are reduced to 5-sulfamoyl-6-halo-3-oxoisoindole compounds bearing a substituted 1-phenylalkyl-4-piperidinyl moiety as the isoindole N-substituent. Preferred compounds such as 6-chloro-2,3-dihydro-3-oxo-2-[1-(phenylmethyl)-4-piperidinyl]-1H-isoindole -5-sulfonamide exhibit diuretic and antihypertensive properties.

  新型邻苯二甲酰亚胺中间体被还原为携带取代的1-苯基烷基-4-哌啶基团作为异吲哚N-取代基的5-磺胺基-6-卤代-3-酮异吲哚化合物。首选化合物，如6-氯-2,3-二氢-3-酮-2-[1-(苯基甲基)-4-哌啶基]-1H-异吲哚-5-磺胺酰胺，具有利尿和降压作用。