9-fluoro-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-amine hydrochloride | 1607472-76-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 9-fluoro-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-amine hydrochloride
• 英文别名: 12-Fluorotetracyclo[8.3.1.18,12.02,7]pentadeca-2,4,6-trien-10-amine;hydrochloride；12-fluorotetracyclo[8.3.1.18,12.02,7]pentadeca-2,4,6-trien-10-amine;hydrochloride
• CAS: 1607472-76-3
• 化学式: C₁₅H₁₈FN*ClH
• 分子量: 267.774
• InChiKey: WLRJZNUCVMVJGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.67
• 重原子数：
  18.0
• 可旋转键数：
  0.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  26.02
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  9-fluoro-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-amine hydrochloride 在 磷酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium iodide 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Searching for novel applications of the benzohomoadamantane scaffold in medicinal chemistry: Synthesis of novel 11β-HSD1 inhibitors

  摘要：

  The structural and physicochemical properties of the adamantane nucleus account for its use as a chemical scaffold in multiple drugs. In the last years, we have developed new polycyclic scaffolds as surrogates of the adamantane group with encouraging results in multiple targets. As adamantane is a common structural feature in several 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) inhibitors, we have explored the ability of the 6,7,8,9,10,11-hexahydro-5H-5,9: 7,11-dimethanobenzo[9]annulen-7-yl scaffold to act as a surrogate of the adamantane nucleus in a novel series of 11 beta-HSD1 inhibitors. Of note, within this family of compounds one derivative is endowed with submicromolar 11 beta-HSD1 inhibitory activity. Molecular modeling studies support the binding of the compounds to the active site of the enzyme. However, a fine tuning of the hydrophobicity of the size-expanded nucleus may be beneficial for the inhibitory potency. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.004
• 作为产物：
  描述：

  9-fluoro-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-amine 在 hydrochloric acid diethyl ether 作用下， 以 二氯甲烷 为溶剂， 生成 9-fluoro-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo[9]annulen-7-amine hydrochloride
  参考文献：
  名称：

  Antibacterial activity of novel benzopolycyclic amines

  摘要：

  Staphylococcus aureus, especially strains resistant to multiple antibiotics, is a major pathogen for humans and animals. In this paper we have synthesized and evaluated the antibacterial activity of a new series of benzopolycyclic amines. Some of them exhibited mu M MIC values against Staphylococcus aureus and other bacteria, including methicillin-resistant S. aureus MRSA. Compound 8 that displayed a good selectivity index, showed to be active in eliminating bacterial cells forming a preexisting biofilm. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.041

文献信息

• From the Design to the <i>In Vivo</i> Evaluation of Benzohomoadamantane-Derived Soluble Epoxide Hydrolase Inhibitors for the Treatment of Acute Pancreatitis
  作者：Sandra Codony、Carla Calvó-Tusell、Elena Valverde、Sílvia Osuna、Christophe Morisseau、M. Isabel Loza、José Brea、Concepción Pérez、María Isabel Rodríguez-Franco、Javier Pizarro-Delgado、Rubén Corpas、Christian Griñán-Ferré、Mercè Pallàs、Coral Sanfeliu、Manuel Vázquez-Carrera、Bruce D. Hammock、Ferran Feixas、Santiago Vázquez

  DOI：10.1021/acs.jmedchem.0c01601

  日期：2021.5.13

  The pharmacological inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Numerous potent sEH inhibitors (sEHIs) present adamantyl or phenyl moieties, such as the clinical candidates AR9281 or EC5026. Herein, in a new series of sEHIs, these hydrophobic moieties have been merged in a benzohomoadamantane scaffold. Most of the new sEHIs

  可溶性环氧化物水解酶 (sEH) 的药理抑制作用可有效治疗炎症和疼痛相关疾病。许多有效的 sEH 抑制剂 (sEHI) 存在金刚烷基或苯基部分，例如临床候选药物 AR9281 或 EC5026。在此，在一系列新的 sEHI 中，这些疏水部分已合并到苯并高金刚烷支架中。大多数新的sEHI对sEH具有优异的抑制活性。分子动力学模拟表明，在金刚烷支架中添加芳环会在酶中产生构象重排，以稳定苯并高金刚烷核心的芳环。筛选级联使我们能够选择体内候选者雨蛙素诱导的急性胰腺炎小鼠模型的疗效研究。22的给药改善了动物的健康状况并减少了胰腺损伤，表明苯并高金刚烷单元是设计新型 sEHI 的有前途的支架。
• 2-(Piperidin-4-yl)acetamides as Potent Inhibitors of Soluble Epoxide Hydrolase with Anti-Inflammatory Activity
  作者：Juan Martín-López、Sandra Codony、Clara Bartra、Christophe Morisseau、María Isabel Loza、Coral Sanfeliu、Bruce D. Hammock、José Brea、Santiago Vázquez

  DOI：10.3390/ph14121323

  日期：——

  The pharmacological inhibition of soluble epoxide hydrolase (sEH) has been suggested as a potential therapy for the treatment of pain and inflammatory diseases through the stabilization of endogenous epoxyeicosatrienoic acids. Numerous potent sEH inhibitors (sEHI) have been developed, however many contain highly lipophilic substituents limiting their availability. Recently, a new series of benzohomoadamantane-based ureas endowed with potent inhibitory activity for the human and murine sEH was reported. However, their very low microsomal stability prevented further development. Herein, a new series of benzohomoadamantane-based amides were synthetized, fully characterized, and evaluated as sEHI. Most of these amides were endowed with excellent inhibitory potencies. A selected compound displayed anti-inflammatory effects with higher effectiveness than the reference sEHI, TPPU.

  可溶性环氧脂水解酶（sEH）的药理抑制已被提出作为通过稳定内源性环氧三烯酸治疗疼痛和炎症性疾病的潜在疗法。已经开发了许多有效的sEH抑制剂（sEHI），然而许多含有高脂溶性取代基的化合物限制了它们的可用性。最近，报道了一系列基于苯并环辛烷基脲的新型化合物，具有对人类和小鼠sEH的强大抑制活性。然而，它们的低微粒体稳定性阻碍了进一步的开发。在这里，合成了一系列基于苯并环辛烷基酰胺的新化合物，进行了全面的表征，并作为sEHI进行了评估。其中大多数酰胺具有出色的抑制活性。一种选定的化合物显示出抗炎效果，其效果比参考的sEHI TPPU 更高。
• COMPOUNDS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
  申请人：Universitat de Barcelona

  公开号：EP4063348A1

  公开（公告）日：2022-09-28

  The present invention relates to soluble epoxide hydrolase (sEH) inhibitors of formula (I) to processes for their obtention and to their therapeutic indications.

  本发明涉及式(I)的可溶性环氧酶水解酶（sEH）抑制剂，以及其制备过程和治疗适应症。
• Novel benzopolycyclic amines with NMDA receptor antagonist activity
  作者：Elena Valverde、Francesc X. Sureda、Santiago Vázquez

  DOI：10.1016/j.bmc.2014.03.025

  日期：2014.5

  A new series of benzopolycyclic amines active as NMDA receptor antagonists were synthesized. Most of them exhibited increased activity compared with related analogues previously published. All the tested compounds were more potent than clinically approved amantadine and one of them displayed a lower IC50 value than memantine, an anti-Alzheimer's approved drug. (C) 2014 Elsevier Ltd. All rights reserved.