tert-butyl (1-(3-methoxybenzyl)piperidin-4-yl)carbamate | 1286274-23-4

• 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: tert-butyl (1-(3-methoxybenzyl)piperidin-4-yl)carbamate
• 英文别名: tert-butyl N-[1-[(3-methoxyphenyl)methyl]piperidin-4-yl]carbamate
• CAS: 1286274-23-4
• 化学式: C₁₈H₂₈N₂O₃
• mdl: MFCD17014372
• 分子量: 320.432
• InChiKey: DFUVKRDDKXUWOY-UHFFFAOYSA-N

物化性质

• 沸点：
  435.7±40.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.611
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (1-(3-methoxybenzyl)piperidin-4-yl)carbamate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 5-(1,2-dithiolan-3-yl)-N-(1-(3-methoxybenzyl)piperidin-4-yl)pentanamide
  参考文献：
  名称：

  Development of Cholinesterase Inhibitors using 1-Benzyl Piperidin-4-yl (α)-Lipoic Amide Molecules

  摘要：

  合成了一系列混合分子，这些分子由（α）-硫辛酸（ALA）和4-氨基-1-苄基哌啶构成，并评估了它们的体外胆碱酯酶（乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE））抑制活性。尽管母体化合物除了化合物14（对BuChE的$IC_{50}=255.26{\pm}4.41$）之外并未表现出任何对胆碱酯酶（ChE）的抑制活性，但所有混合分子均显示出对BuChE的抑制活性。一些混合化合物也表现出对AChE的抑制活性。具体而言，化合物17被证明对AChE（$IC_{50}=1.75{\pm}0.30{\mu}M$）和BuChE（$IC_{50}=5.61{\pm}1.25{\mu}M$）均为有效抑制剂，其活性与加兰他敏（对AChE的$IC_{50}=1.7{\pm}0.9{\mu}M$和对BuChE的$IC_{50}=9.4{\pm}2.5{\mu}M$）相当。使用化合物17进行的抑制动力学研究表明，AChE为混合抑制类型，而BuChE为非竞争性抑制类型。它对AChE和BuChE的结合亲和力（$K_i$）值分别为$3.8{\pm}0.005{\mu}M$和$7.0{\pm}0.04{\mu}M$。

  DOI：

  10.5012/bkcs.2014.35.6.1681
• 作为产物：
  描述：

  4-叔丁氧羰基氨基哌啶 、 3-甲氧基氯苄 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 tert-butyl (1-(3-methoxybenzyl)piperidin-4-yl)carbamate
  参考文献：
  名称：

  2-Phenylindole and Arylsulphonamide: Novel Scaffolds Bactericidal against Mycobacterium tuberculosis

  摘要：

  A cellular activity-based screen on Mycobacterium tuberculosis (Mtb) H37Rv using a focused library from the AstraZeneca corporate collection led to the identification of 2-phenylindoles and arylsulphonamides, novel antimycobacterial scaffolds. Both the series were bactericidal in vitro and in an intracellular macrophage infection model, active against drug sensitive and drug resistant Mtb clinical isolates, and specific to mycobacteria. The scaffolds showed promising structure-activity relationships; compounds with submicromolar cellular potency were identified during the hit to lead exploration. Furthermore, compounds from both scaffolds were tested for inhibition of known target enzymes or pathways of antimycobacterial drugs including InhA, RNA polymerase, DprE1, topoisomerases, protein synthesis, and oxidative-phosphorylation. Compounds did not inhibit any of the targets suggesting the potential of a possible novel mode of action(s). Hence, both scaffolds provide the opportunity to be developed further as leads and tool compounds to uncover novel mechanisms for tuberculosis drug discovery.

  DOI：

  10.1021/ml5001933

文献信息

• Structure–Activity Relationship, Pharmacological Characterization, and Molecular Modeling of Noncompetitive Inhibitors of the Betaine/γ-Aminobutyric Acid Transporter 1 (BGT1)
  作者：Lars Jørgensen、Anas Al-Khawaja、Stefanie Kickinger、Stine B. Vogensen、Jonas Skovgaard-Petersen、Emil Rosenthal、Nrupa Borkar、Rebekka Löffler、Karsten K. Madsen、Hans Bräuner-Osborne、Arne Schousboe、Gerhard F. Ecker、Petrine Wellendorph、Rasmus P. Clausen

  DOI：10.1021/acs.jmedchem.7b00924

  日期：2017.11.9

  4-dichlorobenzamide 5 (BPDBA) is a noncompetitive inhibitor of the betaine/GABA transporter 1 (BGT1). We here report the synthesis and structure–activity relationship of 71 analogues. We identify 26m as a more soluble 2,4-Cl substituted 3-pyridine analogue with retained BGT1 activity and an improved off-target profile compared to 5. We performed radioligand-based uptake studies at chimeric constructs between BGT1

  N -(1-Benzyl-4-piperidinyl)-2,4-dichlorobenzamide 5 (BPDBA) 是一种甜菜碱/GABA 转运蛋白 1 (BGT1) 的非竞争性抑制剂。我们在这里报告了 71 种类似物的合成和构效关系。我们将26m鉴定为更易溶解的 2,4-Cl 取代的 3-吡啶类似物，与5相比具有保留的 BGT1 活性和改善的脱靶特征. 我们在 BGT1 和 GAT3 之间的嵌合构建体上进行了基于放射性配体的摄取研究、定点突变转运蛋白实验以及基于新确定的人血清素转运蛋白 (hSERT) 的 X 射线晶体结构的 BGT1 同源模型中的计算对接。在这些实验的基础上，我们提出了一种结合模式，该模式涉及 BGT1 中变构位点中 TM10 内的残基，该位点对应于 hSERT 晶体结构所揭示的变构结合袋。我们的研究为 BGT1 中提出的变构结合袋提供了初步见解，该袋可容纳一系列新型非竞争性抑制剂的结合位点。
• Discovery and Biological Evaluation of <i>N</i>-Methyl-pyrrolo[2,3-<i>b</i>]pyridine-5-carboxamide Derivatives as JAK1-Selective Inhibitors
  作者：Eunsun Park、Sun Joo Lee、Heegyum Moon、Jongmi Park、Hyeonho Jeon、Ji Sun Hwang、Hayoung Hwang、Ki Bum Hong、Seung-Hee Han、Sun Choi、Soosung Kang

  DOI：10.1021/acs.jmedchem.0c01026

  日期：2021.1.28

  binding modes of current JAK inhibitors to JAK isoforms allowed the design of N-alkyl-substituted 1-H-pyrrolo[2,3-b] pyridine carboxamide as a JAK1-selective scaffold, and the synthesis of various methyl amide derivatives provided 4-((cis-1-(4-chlorobenzyl)-2-methylpiperidin-4-yl)amino)-N-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxamide (31g) as a potent JAK1-selective inhibitor. In particular, the (S,S)-enantiomer

  Janus激酶1（JAK1）在大多数细胞因子介导的通过JAK / STAT信号传导的炎症和自身免疫反应中起关键作用；因此，抑制JAK1是对几种疾病的有前途的治疗策略。分析目前的JAK抑制剂与JAK同工型的结合方式，可以设计N-烷基取代的1- H-吡咯并[2,3- b ]吡啶羧酰胺作为JAK1选择性骨架，并合成各种甲基酰胺衍生物提供了4-（（顺式-1-（4-氯苄基）-2-甲基哌啶-4-基）氨基）-N-甲基-1H-吡咯并[2,3 - b ]吡啶-5-甲酰胺（31g），一种有效的JAK1选择性抑制剂。特别是（31 g（38a）的S，S） -对映异构体对JAK1表现出出色的效力，并具有超过JAK2，JAK3和TYK2的选择性。在研究31g对肝纤维化的作用时，发现它降低了TGF-β诱导的肝星状细胞（HSCs）的增殖和纤维生成基因表达。具体而言，在伤口愈合试验中，31g显着抑制TGF-β诱导的0.25μMHSC迁移。
• 신규한 리포익산／4-아미노 벤질 피페리딘 컨쥬게이트 화합물 및 그의 용도
  申请人：Hanbat National University Industry-Academic Cooperation Foundation 한밭대학교 산학협력단(220040246965) BRN ▼314-82-09226

  公开号：KR101548927B1

  公开（公告）日：2015-09-02

  본 발명은 항산화제인 리포익산과 4-아미노벤질피페리딘 유도체를 컨쥬게이트시킨 신규 리포익산/4-아미노 벤질 피페리딘 컨쥬게이트(conjugated) 화합물 및 이를 함유하는 알츠하이머병 또는 퇴행성 질환의 예방 또는 치료용 약제학적 조성물 및 건강보조식품 조성물에 관한 것이다. 본 발명에 따른 리포익산/4-아미노 벤질 피페리딘 컨쥬게이트(conjugated) 화합물은 아세틸콜린에스터라제(AChE; acetylcholinesterase) 및 부티릴콜린에스터라제(BuChE; butyrylcholinesterase)의 콜린에스터라제(ChE; cholinesterase)에 대한 저해 활성을 나타내어 알츠하이머병 또는 퇴행성 질환의 예방 또는 치료에 있어 효과적인 물질이다. 본 발명의 약제학적 조성물은 콜린에스터라제(ChE)의 활성을 저해하는 리포익산/4-아미노 벤질 피페리딘 컨쥬게이트(conjugated) 화합물을 유효성분으로 함유하여 알츠하이머병 또는 퇴행성 질환의 예방 및 치료에 사용할 수 있을 뿐만 아니라, 알츠하이머병 또는 퇴행성 질환을 개선시키거나 학습능력 및 기억력을 개선시키는 건강보조식품으로도 활용 가능하다.

  本发明涉及将抗氧化剂磷酸脂和4-氨基苯甲基哌啶衍生物共轭成新型磷酸脂/4-氨基苯甲基哌啶共轭化合物以及用于预防或治疗阿尔茨海默病或退行性疾病的药学组合物和保健食品组合物。根据本发明，磷酸脂/4-氨基苯甲基哌啶共轭化合物表现出对乙酰胆碱酯酶(AChE；乙酰胆碱酯酶)和丁酰胆碱酯酶(BuChE；丁酰胆碱酯酶)的胆碱酯酶(ChE；胆碱酯酶)的抑制活性，是阿尔茨海默病或退行性疾病的预防或治疗中有效的物质。本发明的药学组合物含有抑制胆碱酯酶活性的磷酸脂/4-氨基苯甲基哌啶共轭化合物作为有效成分，可用于预防和治疗阿尔茨海默病或退行性疾病，同时也可作为改善阿尔茨海默病或退行性疾病、提高学习能力和记忆力的保健食品。
• Synthesis and Preliminary Biological Evaluation of New Phthalazinone Derivatives with PARP-1 and Cholinesterase Inhibitory Activities
  作者：Zhenli Min、Yu Lin、Chengzhi Gao、Zhuyong Wang、Ruifeng Zhang、Yajun Chen

  DOI：10.2174/1570180819666220531144809

  日期：2023.1

  hydrophobic interactions, which were necessary for hBChE inhibitory potency. Conclusion: A new compound with potent PARP-1 inhibitory activity and moderate BChE inhibitory activity was obtained, which merited to be further investigated as an anti-AD drug. The studies gave a clue to search for new agents based on PARP-1 and cholinesterase dual-inhibited activities to treat AD.

  背景：阿尔茨海默氏病 (AD) 是最常见的脑部疾病，并且仍然是全世界的主要健康问题。考虑到 AD 的高度复杂机制，寻找基于多靶点定向配体 (MTDLs) 策略治疗 AD 的药物可能比传统的“一种药物-一种靶点”策略更有前景。抑制聚（ADP-核糖）聚合酶-1 (PARP-1) 对 AD 具有潜在的治疗作用。因此，值得研究同时靶向 PARP-1 和胆碱酯酶的化合物，这可能会产生新的抗 AD 药物。目的：寻找具有 PARP-1 和胆碱酯酶抑制活性的新药治疗 AD。方法：一系列 21 种新化合物结合了两种上市药物的各自药效团，即 PARP-1 抑制剂的 4-苄基酞嗪酮部分，Olaparib 和 AChE 抑制剂多奈哌齐的 Nbenzylpiperidine 部分被合成到一个分子中。评估了所有合成化合物对酶 PARP-1、乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BChE) 的抑制活性。通过分子对接研究了
• 2-Phenylindole and Arylsulphonamide: Novel Scaffolds Bactericidal against <i>Mycobacterium tuberculosis</i>
  作者：Maruti Naik、Sandeep Ghorpade、Lalit Kumar Jena、Gopinath Gorai、Ashwini Narayan、Supreeth Guptha、Sreevalli Sharma、Neela Dinesh、Parvinder Kaur、Radha Nandishaiah、Jyothi Bhat、Gayathri Balakrishnan、Vaishali Humnabadkar、Vasanthi Ramachandran、Lava Kumar Naviri、Pallavi Khadtare、Manoranjan Panda、Pravin S. Iyer、Monalisa Chatterji

  DOI：10.1021/ml5001933

  日期：2014.9.11

  A cellular activity-based screen on Mycobacterium tuberculosis (Mtb) H37Rv using a focused library from the AstraZeneca corporate collection led to the identification of 2-phenylindoles and arylsulphonamides, novel antimycobacterial scaffolds. Both the series were bactericidal in vitro and in an intracellular macrophage infection model, active against drug sensitive and drug resistant Mtb clinical isolates, and specific to mycobacteria. The scaffolds showed promising structure-activity relationships; compounds with submicromolar cellular potency were identified during the hit to lead exploration. Furthermore, compounds from both scaffolds were tested for inhibition of known target enzymes or pathways of antimycobacterial drugs including InhA, RNA polymerase, DprE1, topoisomerases, protein synthesis, and oxidative-phosphorylation. Compounds did not inhibit any of the targets suggesting the potential of a possible novel mode of action(s). Hence, both scaffolds provide the opportunity to be developed further as leads and tool compounds to uncover novel mechanisms for tuberculosis drug discovery.