(2-oxaadamantan-1-yl)amine hydrochloride | 16193-06-9

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: (2-oxaadamantan-1-yl)amine hydrochloride
• 英文别名: 2-oxaadamantyl-1-amine hydrochloride；(2-oxaadamant-1-yl)amine hydrochloride；(1r,3s,5R,7S)-2-Oxaadamantan-1-amine hydrochloride；2-oxatricyclo[3.3.1.13,7]decan-1-amine;hydrochloride
• CAS: 16193-06-9
• 化学式: C₉H₁₅NO*ClH
• 分子量: 189.685
• InChiKey: YEWFFFAYPIELAC-UHFFFAOYSA-N

物化性质

• 熔点：
  280 °C

计算性质

• 辛醇/水分配系数(LogP)：
  1.67
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  35.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2-oxaadamantan-1-yl)amine hydrochloride 在 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 三乙胺 作用下， 以 盐酸 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 120.5h， 生成 1-(2-oxaadamant-1-yl)-3-(1-(isopropylsulfonyl)piperidin-4-yl)-urea
  参考文献：
  名称：

  [EN] ANALOGS OF ADAMANTYLUREAS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
  [FR] ANALOGUES D'ADAMANTYLURÉES UTILISÉS EN TANT QU'INHIBITEURS D'HYDROLASE ÉPOXYDE SOLUBLE

  摘要：

  式I的N-(2-氧杂孔莫烷-1-基)脲，其中R3为H、C1-C3烷基、环己基或苯基；R为-[CH2]n-Y；n为0-15；在-[CH2]n-中，0-n/3的亚甲基基团可选择性地被非相邻的氧原子取代；Y为3-或4-取代苯基、3-或4-取代环己基、N-取代哌啶-4-基、N-取代哌啶-3-基、二氟或三氟取代苯基、4-氯-3-三氟甲基苯基、3-氯-4-三氟甲基苯基、4-氟-3-三氟甲基苯基或3-氟-4-三氟甲基苯基；具有环氧化酶（sEH）抑制活性，类似于其N-(孔莫烷-1-基)脲类似物。因此，化合物I可用作治疗sEH介导疾病的API。此外，一般而言，化合物（I）具有较高的水溶性和较低的熔点，这使它们在药代动力学和配方方面更具有前景。

  公开号：

  WO2017017048A1
• 作为产物：
  描述：

  (1r,3s,5R,7S)-2-oxaadamantan-1-amine 在 盐酸 作用下， 以 甲醇 为溶剂， 以1.05 g的产率得到(2-oxaadamantan-1-yl)amine hydrochloride
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of (2-oxaadamant-1-yl)amines

  摘要：

  The synthesis of several (2-oxaadamant-1-yl) amines is reported. They were evaluated as NMDA receptor antagonists and several of them were more active than amantadine, but none was more potent than memantine. None of the tested compounds displayed antiviral activity. Two of the derivatives showed a significant level of trypanocidal activity. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.02.007

文献信息

• 2-Oxaadamant-1-yl Ureas as Soluble Epoxide Hydrolase Inhibitors: <i>In Vivo</i> Evaluation in a Murine Model of Acute Pancreatitis
  作者：Sandra Codony、Eugènia Pujol、Javier Pizarro、Ferran Feixas、Elena Valverde、M. Isabel Loza、José M. Brea、Elena Saez、Julen Oyarzabal、Antonio Pineda-Lucena、Belén Pérez、Concepción Pérez、María Isabel Rodríguez-Franco、Rosana Leiva、Sílvia Osuna、Christophe Morisseau、Bruce D. Hammock、Manuel Vázquez-Carrera、Santiago Vázquez

  DOI：10.1021/acs.jmedchem.0c00310

  日期：2020.9.10

  In vivo pharmacological inhibition of soluble epoxide hydrolase (sEH) reduces inflammatory diseases, including acute pancreatitis (AP). Adamantyl ureas are very potent sEH inhibitors, but the lipophilicity and metabolism of the adamantane group compromise their overall usefulness. Herein, we report that the replacement of a methylene unit of the adamantane group by an oxygen atom increases the solubility, permeability, and stability of three series of urea-based sEH inhibitors. Most of these oxaanalogues are nanomolar inhibitors of both the human and murine sEH. Molecular dynamics simulations rationalize the molecular basis for their activity and suggest that the presence of the oxygen atom on the adamantane scaffold results in active site rearrangements to establish a weak hydrogen bond. The 2-oxaadamantane 22, which has a good solubility, microsomal stability, and selectivity for sEH, was selected for further in vitro and in vivo studies in models of cerulein-induced AP. Both in prophylactic and treatment studies, 22 diminished the overexpression of inflammatory and endoplasmic reticulum stress markers induced by cerulein and reduced the pancreatic damage.
• ANALOGS OF ADAMANTYLUREAS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
  申请人：Universitat de Barcelona

  公开号：EP3328854A1

  公开（公告）日：2018-06-06