4,4-二乙基哌啶 | 3970-64-7

• 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: 4,4-二乙基哌啶
• 英文名称: 4,4-Diethyl-piperidin
• 英文别名: 4,4-diethyl-piperidine；4,4-Diethylpiperidine
• CAS: 3970-64-7
• 化学式: C₉H₁₉N
• 分子量: 141.257
• InChiKey: DGZSVBBLLGZHSF-UHFFFAOYSA-N

物化性质

• 沸点：
  172.9±8.0 °C(Predicted)
• 密度：
  0.802±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4,4-二乙基哌啶 、 (4-chloro-6-fluoroquinolin-3-yl)(4-(cyclopropanecarbonyl)piperazin-1-yl)methanone 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (4-(cyclopropanecarbonyl)piperazin-1-yl)(4-(4,4-diethylpiperidin-1-yl)-6-fluoroquinolin-3-yl)methanone
  参考文献：
  名称：

  Discovery of Orally Bioavailable, Quinoline-Based Aldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors with Potent Cellular Activity

  摘要：

  Aldehyde dehydrogenases (ALDHs) are responsible for the metabolism of aldehydes (exogenous and endogenous) and possess vital physiological and toxicological functions in areas such as CNS, inflammation, metabolic disorders, and cancers. Overexpression of certain ALDHs (e.g., ALDHIAI) is an important biomarker in cancers and cancer stem cells (CSCs) indicating the potential need for the identification and development of small molecule ALDH inhibitors. Herein, a newly designed series of quinoline-based analogs of ALDH1A1 inhibitors is described. Extensive medicinal chemistry optimization and biological characterization led to the identification of analogs with significantly improved enzymatic and cellular ALDH inhibition. Selected analogs, e.g., 86 (NCT-505) and 91 (NCT-506), demonstrated target engagement in a cellular thermal shift assay (CETSA), inhibited the formation of 3D spheroid cultures of OV-90 cancer cells, and potentiated the cytotoxicity of paclitaxel in SKOV-3-TR, a paclitaxel resistant ovarian cancer cell line. Lead compounds also exhibit high specificity over other ALDH isozymes and unrelated dehydrogenases. The in vitro ADME profiles and pharmacokinetic evaluation of selected analogs are also highlighted.

  DOI：

  10.1021/acs.jmedchem.8b00270

文献信息

• CYCLOALKYLIDENE AND HETEROCYCLOALKYLIDENE INHIBITOR COMPOUNDS
  申请人：Melvin, JR. Lawrence S.

  公开号：US20100022543A1

  公开（公告）日：2010-01-28

  The present invention provides a compound of general Formula (I) having histone deacetylase (HDAC) inhibitory activity, a pharmaceutical composition comprising the compound, and a method useful to treat diseases using the compound.

  本发明提供了一种具有组蛋白去乙酰化酶（HDAC）抑制活性的一般式（I）化合物，包括该化合物的药物组合物，以及使用该化合物治疗疾病的方法。
• [EN] siRNAs WITH AT LEAST TWO LIGANDS AT DIFFERENT ENDS<br/>[FR] ARNSI POSSÉDANT AU MOINS DEUX LIGANDS À DEUX EXTRÉMITÉS DISTINCTES
  申请人：SILENCE THERAPEUTICS GMBH

  公开号：WO2019193189A1

  公开（公告）日：2019-10-10

  There is provided inter alia a conjugate for inhibiting expression of a target gene in a cell, said conjugate comprising a nucleic acid portion and ligand portions, said nucleic acid portion comprising at least one duplex region that comprises at least a portion of a first RNA strand and at least a portion of a second RNA strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from said target gene, said ligand portions comprising a linker moiety and a targeting ligand for in vivo targeting of cells and being conjugated exclusively to the 3' and/or 5' ends of one or both RNA strands, wherein the 5' end of the first RNA strand is not conjugated, wherein: (i) the second RNA strand is conjugated at the 5' end to the targeting ligand, and wherein (a) the second RNA strand is also conjugated at the 3' end to the targeting ligand and the 3' end of the first RNA strand is not conjugated; or (b) the first RNA strand is conjugated at the 3' end to the targeting ligand and the 3' end of the second RNA strand is not conjugated; or (c) both the second RNA strand and the first RNA strand are also conjugated at the 3' ends to the targeting ligand; or (ii) both the second RNA strand and the first RNA strand are conjugated at the 3' ends to the targeting ligand and the 5' end of the second RNA strand is not conjugated.

  提供了一种用于抑制细胞中靶基因表达的共轭物，该共轭物包括核酸部分和配体部分，所述核酸部分包括至少一个双链区域，该区域包括至少部分第一RNA链和至少部分第二RNA链，该第二RNA链至少部分与第一链互补，其中所述第一链至少部分与从所述靶基因转录的RNA的至少部分互补，所述配体部分包括连接子基团和用于体内细胞靶向的靶向配体，并且仅连接到一个或两个RNA链的3'和/或5'末端，其中第一RNA链的5'末端未连接，其中：(i) 第二RNA链在5'末端连接到靶向配体，其中(a) 第二RNA链还在3'末端连接到靶向配体，且第一RNA链的3'末端未连接；或(b) 第一RNA链在3'末端连接到靶向配体，且第二RNA链的3'末端未连接；或(c) 第二RNA链和第一RNA链的3'末端均连接到靶向配体；或(ii) 第二RNA链和第一RNA链的3'末端均连接到靶向配体，且第二RNA链的5'末端未连接。
• [EN] MACROCYCLIC FUSED PYRRAZOLES AS MCL-1 INHIBITORS<br/>[FR] PYRRAZOLES FUSIONNÉS MACROCYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE MCL-1
  申请人：ASCENTAGE PHARMA SUZHOU CO LTD

  公开号：WO2020151738A1

  公开（公告）日：2020-07-30

  Provided are compounds represented by Formula IA: (IA), and the pharmaceutically acceptable salts and solvates thereof, wherein R, R 1a, R 1b, L 1, L 2, L 3, X, A, B and C are as defined as set forth in the specification. Also provided compounds of Formula IA for use to treat a condition or disorder responsive to Mcl-1 inhibition such as cancer.

  提供由化学式IA表示的化合物，以及其在药学上可接受的盐和溶剂化合物，其中R、R 1a、R 1b、L 1、L 2、L 3、X、A、B和C的定义如规范中所述。还提供了化学式IA的化合物，用于治疗对Mcl-1抑制敏感的疾病或紊乱，如癌症。
• [EN] NUCLEIC ACIDS FOR INHIBITING EXPRESSION OF PROS1 IN A CELL<br/>[FR] ACIDES NUCLÉIQUES POUR INHIBER L'EXPRESSION DE PROS1 DANS UNE CELLULE
  申请人：UNIV BERN

  公开号：WO2020225301A1

  公开（公告）日：2020-11-12

  The invention relates to nucleic acid products that interfere with PROS1 gene expression or inhibit its expression. The nucleic acids are particularly for use in the treatment, prevention or reduction of risk of suffering from a bleeding disorder.

  该发明涉及干扰PROS1基因表达或抑制其表达的核酸产品。这些核酸特别用于治疗、预防或减少患出血障碍的风险。
• [EN] NUCLEIC ACIDS FOR INHIBITING EXPRESSION OF CNNM4 IN A CELL<br/>[FR] ACIDES NUCLÉIQUES POUR INHIBER L'EXPRESSION DE CNNM4 DANS UNE CELLULE
  申请人：SILENCE THERAPEUTICS GMBH

  公开号：WO2021239825A1

  公开（公告）日：2021-12-02

  The invention relates to nucleic acid products that interfere with or inhibit CNNM4 (Cyclin M4) gene expression. It further relates to therapeutic uses of CNNM4 inhibition for the treatment of diseases, such as liver diseases including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver steatosis, liver fibrosis, liver cirrhosis, liver cancer and other diseases associated with magnesium dysregulation.

  本发明涉及与干扰或抑制CNNM4（Cyclin M4）基因表达有关的核酸产品。它进一步涉及使用CNNM4抑制剂治疗疾病，例如肝病，包括非酒精性脂肪性肝病（NAFLD），非酒精性脂肪性肝炎（NASH），肝脂肪变性，肝纤维化，肝硬化，肝癌和其他与镁离子调节失调有关的疾病。