tert-butyl (1-(benzo[d][1,3]dioxol-5-ylmethyl)piperidin-4-yl)carbamate | 934264-70-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: tert-butyl (1-(benzo[d][1,3]dioxol-5-ylmethyl)piperidin-4-yl)carbamate
• 英文别名: tert-butyl [1-(1,3-benzodioxol-5-ylmethyl)-piperidin-4-yl]carbamate；Tert-butyl [1-(1,3-benzodioxol-5-ylmethyl)piperidin-4-yl]carbamate；tert-butyl N-[1-(1,3-benzodioxol-5-ylmethyl)piperidin-4-yl]carbamate
• CAS: 934264-70-7
• 化学式: C₁₈H₂₆N₂O₄
• 分子量: 334.415
• InChiKey: AEUZYDOXMHACNR-UHFFFAOYSA-N

物化性质

• 沸点：
  452.6±34.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  60
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (1-(benzo[d][1,3]dioxol-5-ylmethyl)piperidin-4-yl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 25.0h， 生成 2-Amino-N-(1-benzo[1,3]dioxol-5-ylmethyl-piperidin-4-yl)-5-chloro-benzamide
  参考文献：
  名称：

  Screening for Cardiovascular Safety:  A Structure−Activity Approach for Guiding Lead Selection of Melanin Concentrating Hormone Receptor 1 Antagonists

  摘要：

  An inactin-anesthetized rat cardiovascular (CV) assay was employed in a screening mode to triage multiple classes of melanin-concentrating hormone receptor I (MCHr1) antagonists. Lead identification was based on a compound profile producing high drug concentration in both plasma (> 40 mu M) and brain (> 20 mu g/g) with < 15% change in cardiovascular endpoints. As a result of these stringent requirements, lead optimization activities on multiple classes of MCHr1 antagonists were terminated. After providing evidence that the cardiovascular liabilities were not a function of MCHr1 antagonism, continued screening identified the chromone-substituted aminopiperidine amides as a class of MCHr1 antagonists that demonstrated a safe cardiovascular profile at high drug concentrations in both plasma and brain. The high incidence of adverse cardiovascular effects associated with an array of MCHrl antagonists of significant chemical diversity, combined with the stringent safety requirements for antiobesity drugs, highlight the importance of incorporating cardiovascular safety assessment early in the lead selection process.

  DOI：

  10.1021/jm0512286
• 作为产物：
  描述：

  胡椒醛 、 4-叔丁氧羰基氨基哌啶 生成 tert-butyl (1-(benzo[d][1,3]dioxol-5-ylmethyl)piperidin-4-yl)carbamate
  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

文献信息

• Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor
  申请人：Lynch K. John

  公开号：US20050209274A1

  公开（公告）日：2005-09-22

  The present invention is directed to compounds of formula (I), which antagonize of the effects of melanin-concentrating hormone (MCH) through the melanin concentrating hormone receptor which is useful for the prevention or treatment of eating disorders, weight gain, obesity, abnormalities in reproduction and sexual behavior, thyroid hormone secretion, diuresis and water/electrolyte homeostasis, sensory processing, memory, sleeping, arousal, anxiety, depression, seizures, neurodegeneration and psychiatric disorders.

  本发明涉及式(I)的化合物，通过对抗黑素浓集激素（MCH）的作用，通过对抗黑素浓集激素受体，有助于预防或治疗进食障碍、体重增加、肥胖、生殖和性行为异常、甲状腺激素分泌、利尿和水/电解质稳态、感觉处理、记忆、睡眠、觉醒、焦虑、抑郁、癫痫、神经退行性疾病和精神障碍。
• 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。
• SUBSTITUTED 1-AMINOPHTHALAZINE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC APPLICATION THEREOF
  申请人：AUGEREAU Jean Michel

  公开号：US20090124624A1

  公开（公告）日：2009-05-14

  The invention concerns 1-amino-phthalazine derivatives of general formula (I): Wherein A, B, L, R, R 1 , R 2 , R 3 , R 4 , R 5 and R 7 are as defined herein. The invention also concerns the preparation of said compounds and their therapeutic use.

  这项发明涉及一般式(I)的1-氨基邻苯二酮衍生物：其中A、B、L、R、R1、R2、R3、R4、R5和R7如本文所定义。该发明还涉及所述化合物的制备及其治疗用途。
• 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。
• Screening for Cardiovascular Safety:  A Structure−Activity Approach for Guiding Lead Selection of Melanin Concentrating Hormone Receptor 1 Antagonists
  作者：Philip R. Kym、Andrew J. Souers、Thomas J. Campbell、John K. Lynch、Andrew S. Judd、Rajesh Iyengar、Anil Vasudevan、Ju Gao、Jennifer C. Freeman、Dariusz Wodka、Mathew Mulhern、Gang Zhao、Seble H. Wagaw、James J. Napier、Sevan Brodjian、Brian D. Dayton、Regina M. Reilly、Jason A. Segreti、Ryan M. Fryer、Lee C. Preusser、Glenn A. Reinhart、Lisa Hernandez、Kennan C. Marsh、Hing L. Sham、Christine A. Collins、James S. Polakowski

  DOI：10.1021/jm0512286

  日期：2006.4.1

  An inactin-anesthetized rat cardiovascular (CV) assay was employed in a screening mode to triage multiple classes of melanin-concentrating hormone receptor I (MCHr1) antagonists. Lead identification was based on a compound profile producing high drug concentration in both plasma (> 40 mu M) and brain (> 20 mu g/g) with < 15% change in cardiovascular endpoints. As a result of these stringent requirements, lead optimization activities on multiple classes of MCHr1 antagonists were terminated. After providing evidence that the cardiovascular liabilities were not a function of MCHr1 antagonism, continued screening identified the chromone-substituted aminopiperidine amides as a class of MCHr1 antagonists that demonstrated a safe cardiovascular profile at high drug concentrations in both plasma and brain. The high incidence of adverse cardiovascular effects associated with an array of MCHrl antagonists of significant chemical diversity, combined with the stringent safety requirements for antiobesity drugs, highlight the importance of incorporating cardiovascular safety assessment early in the lead selection process.