N,4-Dimethyl-4-cyanopiperidin | 62718-29-0

• 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: N,4-Dimethyl-4-cyanopiperidin
• 英文别名: 1,4-dimethyl-piperidine-4-carbonitrile；1,4-Dimethylpiperidine-4-carbonitrile
• CAS: 62718-29-0
• 化学式: C₈H₁₄N₂
• 分子量: 138.213
• InChiKey: QTWQALQTWXMGDT-UHFFFAOYSA-N

物化性质

• 沸点：
  214.1±33.0 °C(Predicted)
• 密度：
  0.96±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N,4-Dimethyl-4-cyanopiperidin 在 吡啶 、 硫化氢 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 4-[2-(1,4-二甲基-哌啶-4-基)-噻唑-4-基]-苯甲酸
  参考文献：
  名称：

  Design and Synthesis of Tri-Ring P₃ Benzamide-Containing Aminonitriles as Potent, Selective, Orally Effective Inhibitors of Cathepsin K

  摘要：

  We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P-2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/ L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.

  DOI：

  10.1021/jm058198r
• 作为产物：
  描述：

  哌啶-4-甲酰胺 在 氯化亚砜 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正庚烷 、 氯仿 、 乙基苯 、 水 为溶剂， 反应 29.0h， 生成 N,4-Dimethyl-4-cyanopiperidin
  参考文献：
  名称：

  Design and Synthesis of Tri-Ring P₃ Benzamide-Containing Aminonitriles as Potent, Selective, Orally Effective Inhibitors of Cathepsin K

  摘要：

  We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P-2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/ L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.

  DOI：

  10.1021/jm058198r

文献信息

• BICYCLIC HETEROCYCLIC DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF
  申请人：Agency for Science, Technology and Research

  公开号：US20140371199A1

  公开（公告）日：2014-12-18

  The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.

  本发明涉及某些化合物（例如咪唑吡嗪、咪唑吡啶、咪唑吡嗪和咪唑嘧啶化合物），这些化合物作为MAP激酶相互作用激酶MNK2a、MNK2b、MNK1a和MNK1b的抑制剂。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物制备用于预防和治疗疾病（例如增生性疾病（例如癌症）、炎症性疾病、阿尔茨海默病）的药物的用途，以及治疗这些疾病的方法。
• Protein Modification at Tyrosine with Iminoxyl Radicals
  作者：Katsuya Maruyama、Takashi Ishiyama、Yohei Seki、Kentaro Sakai、Takaya Togo、Kounosuke Oisaki、Motomu Kanai

  DOI：10.1021/jacs.1c09066

  日期：2021.12.1

  acids can mimic PTMs. However, reversible SPMs at hydrophobic amino acid residues in proteins are especially limited. Here, we report a tyrosine (Tyr)-selective SPM utilizing persistent iminoxyl radicals, which are readily generated from sterically hindered oximes via single-electron oxidation. The reactivity of iminoxyl radicals with Tyr was dependent on the steric and electronic demands of oximes;

  蛋白质的翻译后修饰 (PTM) 是一种可逆地控制蛋白质功能的生物学机制。特定规范氨基酸的合成蛋白修饰 (SPM) 可以模拟 PTM。然而，蛋白质中疏水氨基酸残基上的可逆 SPM 尤其有限。在这里，我们报告了一种酪氨酸 (Tyr) 选择性 SPM，它利用持久的亚氨基氧基自由基，这些自由基很容易通过单电子氧化从空间位阻肟生成。亚氨氧基自由基与 Tyr 的反应性取决于肟的空间和电子需求；异丙基甲基哌啶肟1f形成稳定的加合物，而叔丁基甲基哌啶肟1o的反应是可逆的。1f和1o之间的可逆性差异（仅由一个甲基区分）是由于亚氨基氧基自由基的稳定性，这部分取决于肟 O-H 基团的键解离能。用1f和1o进行的 Tyr 选择性修饰是在生理相关的温和条件下进行的。具体来说，用1f进行的稳定 Tyr 修饰将功能性小分子（包括偶氮苯光开关）引入蛋白质。此外，通过 SPM 用1o掩盖关键的 Tyr 残基，以及随后由硫醇
• [EN] [1, 2, 4] TRIAZOLO [1, 5-A] PYRIDINES AS JAK INHIBITORS<br/>[FR] [1, 2, 4]TRIAZOLO[1, 5-A]PYRIDINES UTILISÉES COMME INHIBITEURS DE JAK
  申请人：GALAPAGOS NV

  公开号：WO2010010184A1

  公开（公告）日：2010-01-28

  Novel [1,2,4]triazolo[1,5-a]pyridine compounds are disclosed that have a Formula represented by the following: (I). The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, joint disease, inflammation, and others.

  揭示了一种具有以下式表示的化学式的新型[1,2,4]三唑并[1,5-a]吡啶化合物（I）。这些化合物可以制备为药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的各种疾病，例如关节疾病、炎症等。
• Cannabinoid receptor ligands and uses thereof
  申请人：Pfizer Inc

  公开号：US20040157839A1

  公开（公告）日：2004-08-12

  Compounds of Formula (I) that act as cannabinoid receptor ligands and their uses in the treatment of diseases linked to the mediation of the cannabinoid receptors in animals are described herein. 1

  化合物的化学式（I），其作为大麻素受体配体并在治疗与动物体内大麻素受体介导相关疾病中的用途被描述在此。
• HETEROCYCLIC COMPOUNDS AS PI3K-y INHIBITORS
  申请人：Incyte Corporation

  公开号：US20170129899A1

  公开（公告）日：2017-05-11

  This application relates to compounds of Formula (I): or pharmaceutically acceptable salts or stereoisomers thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.

  该申请涉及式(I)的化合物，或其药用盐或立体异构体，这些化合物是PI3K-γ的抑制剂，对于治疗自身免疫性疾病、癌症、心血管疾病和神经退行性疾病等疾病有用。