2,4,10-trioxaadamantane | 281-32-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,4,10-trioxaadamantane
• 英文别名: trioxaadamantane；2,4,10-trioxa-adamantane；2,4,10-Trioxa-adamantan；2,4,10-Trioxaadamantan；2,8,9-Trioxaadamantan；Trioxa-adamantan；2,4,10-trioxatricyclo[3.3.1.13,7]decane
• CAS: 281-32-3
• 化学式: C₇H₁₀O₃
• 分子量: 142.155
• InChiKey: VUIDKQHXAUDXKD-UHFFFAOYSA-N

物化性质

• 沸点：
  190.2±20.0 °C(Predicted)
• 密度：
  1.262±0.06 g/cm3(Predicted)
• 熔点：
  219-220 °C

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  10
• 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：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,4,10-trioxaadamantane 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成
  参考文献：
  名称：

  Bouab, Otmane; Lamaty, Gerard; Moreau, Claude, Canadian Journal of Chemistry, 1980, vol. 58, p. 567 - 573

  摘要：

  DOI：
• 作为产物：
  描述：

  CIS,CIS-1,3,5-CYCLOHEXANETRIOL DIHYDRATE 、 原甲酸三甲酯 在 混旋樟脑磺酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以83 %的产率得到2,4,10-trioxaadamantane
  参考文献：
  名称：

  Adamantoid Scaffolds for Multiple Cargo Loading and Cellular Delivery as β‐Cyclodextrin Inclusion Complexes

  摘要：

  摘要开发能结合β-CD并能轭合多种载体进行细胞递送的载体有着巨大的需求。我们合成了三氧杂金刚烷衍生物，每种客体最多可结合三种载体。1H NMR 滴定法和等温滴定量热法显示，这些客体能与β-CD 形成 1 ：1 的包合物，其结合常数约为 103 M-1。通过单晶测定，β-CD 与客体的共结晶产生了 1 ：1 的包合物晶体。在所有情况下，三氧杂金刚烷核心都埋藏在β-CD的疏水空腔中，三个羟基暴露在外面。我们利用具有代表性的候选 G4 及其与 β-CD（β-CD⊂G4）的包合复合物，通过使用 HeLa 细胞进行 MTT 试验，确定了它们的生物相容性。我们用罗丹明共轭 G4 培养 HeLa 细胞，并通过共聚焦激光扫描显微镜（CLSM）和荧光激活细胞分拣（FACS）分析确定了细胞货物运输。为了进行功能测试，我们用 G4 衍生的原药 G6 和 G7 的 β-CD 包合复合物培养 HeLa 细胞，这两种原药分别含有一个和三个单位的抗肿瘤药物（S）-(+)-喜树碱。用β-CD⊂G7培养的细胞显示出最高的喜树碱内化率和均匀分布。与G7、喜树碱、G6和β-CD⊂G6相比，β-CD⊂G7显示出更高的细胞毒性，这肯定了金刚烷类衍生物在高密度负载和货物运输方面的效率。

  DOI：

  10.1002/anie.202307324

文献信息

• Dual modulation of endocannabinoid transport and fatty-acid amide hydrolase for treatment of excitotoxicity
  申请人：Bahr Ben A.

  公开号：US20100234379A1

  公开（公告）日：2010-09-16

  The endocannabinoid transporter and FAAH are sites of modulation that allow pharmacological enhancement of protective endocannabinergic signals. Selective inhibitors of the transporter and inhibitors of FAAH caused additive augmentation of endogenous signaling events mediated by the cannabinoid CB1 receptor. Disruption of such signals has been shown to prevent neuronal maintenance processes and increase vulnerability to brain damage. Here, blocking endocannabinoid inactivation enhanced cannabinergic activity and ameliorated cellular disturbances associated with excitotoxicity. Modulating the endocannabinoid system in this way also prevented excitotoxic behavioral abnormalities including memory impairment. Collectively, these results indicate that increasing endocannabinoid responses by inhibiting the endocannabinoid transported and/or the inhibiting FAAH leads to molecular, cellular, and functional protection against excitotoxic insults like stroke and traumatic brain injury.

  内源大麻素转运体和FAAH是调节的位点，允许药物增强保护性内源大麻素信号。选择性转运体抑制剂和FAAH抑制剂导致通过大麻素CB1受体介导的内源信号事件的加成增强。破坏这种信号已被证明可以防止神经维持过程并增加对脑损伤的脆弱性。在这里，阻断内源大麻素失活增强了大麻活性，并改善了与兴奋毒性相关的细胞紊乱。以这种方式调节内源大麻素系统还可以预防兴奋毒性行为异常，包括记忆障碍。总的来说，这些结果表明，通过抑制内源大麻素转运体和/或抑制FAAH来增加内源大麻素反应，可以在分子、细胞和功能上保护免受像中风和创伤性脑损伤等兴奋毒性侵害。
• [EN] NOVEL HETERO PYRROLE ANALOGS ACTING ON CANNAPINOID RECEPTORS<br/>[FR] NOUVEAUX ANALOGUES HÉTÉROPYRROLES AGISSANT SUR LES RÉCEPTEURS CANNABINOÏDES
  申请人：UNIV CONNECTICUT

  公开号：WO2010104488A1

  公开（公告）日：2010-09-16

  Disclosed are biologically active hetero pyrrole analogs such as imidazoles, thiazoles, oxazoles and pyrazoles capable of interacting with the CB1 and/or CB2 cannabinoid receptors. Aspects disclose hetero pyrrole analogs acting as CB1 and/or CB 1 receptor antagonists, having selectivity for the CB 1 or CB2 receptor, acting as neutral antagonists, acting preferentially on CB 1 receptors located in the peripheral nervous system, and/or acting as nitric oxide donors. Pharmaceutical preparations employing the disclosed analogs and methods of administering therapeutically effective amounts of the disclosed analogs to provide a physiological effect are also disclosed.

  本文披露了生物活性的杂环吡咯类似物，如咪唑、噻唑、噁唑和吡唑，能够与CB1和/或CB2大麻素受体相互作用。本文披露了作为CB1和/或CB 1受体拮抗剂的杂环吡咯类似物，具有对CB 1或CB2受体的选择性，作为中性拮抗剂，首选作用于外周神经系统中的CB 1受体，和/或作为一氧化氮供体的作用。还披露了使用披露的类似物的药物制剂和通过给予治疗有效量的披露的类似物以提供生理效应的方法。
• Compounds for Treating Cannabinoid Toxicity and Acute Cannabinoid Overdose
  申请人：MAKScientific, LLC

  公开号：US20220033393A1

  公开（公告）日：2022-02-03

  The present invention relates to novel compounds that can act as antidotes for treating “Acute Cannabinoid Overdose” produced by classical cannabinoids such as Δ 9 -tetrahydrocannabinol (THC) and several synthetic psychoactive cannabinoids (SPCs). The cannabis constituent THC exerts its psychotropic effects via CB1 receptor activation and SPCs mimic the effects of THC with higher potency and severe neurotoxicity. Compounds disclosed in this invention, their enantiomers, diastereomers, geometric isomers, racemates, tautomers, rotamers, atropisomers, metabolites, N-oxides, salts, solvates, hydrates, isotopic variations and their polymorphic forms can be therapeutically useful in an emergency setting for counteracting the intoxicating effects of acute THC ingestion and SPC overdose. Also, aspects of the invention are concerned with pyrazoles, imidazoles, triazoles, thiazoles, oxazoles, dihydropyrazoles, pyrrolidinones, azetidines, oxyazetidines and azaspiro[3.3]heptanes with unique pharmacokinetic and pharmacodynamic properties for treating “Acute Cannabinoid Overdose”.

  本发明涉及一种新型化合物，可以作为治疗由经典大麻素（如Δ9-四氢大麻酚（THC））和几种合成精神活性大麻素（SPCs）产生的“急性大麻素过量”的解毒剂。大麻成分THC通过CB1受体激活发挥其精神活性作用，而SPCs则模拟THC的效果，具有更高的效力和严重的神经毒性。本发明披露的化合物及其对映体、二对映体、几何异构体、拉克酸盐、互变异构体、转型异构体、异构异构体、代谢物、N-氧化物、盐、溶剂合物、水合物、同位素变体及其多态形式在急诊情况下可以在对抗急性THC摄入和SPC过量的中毒作用方面具有治疗用途。此外，本发明涉及吡唑烷、咪唑烷、三唑烷、噻唑烷、噁唑烷、二氢吡唑烷、吡咯烷酮、氮杂环丁烷、氧杂环丁烷和氮杂螺[3.3]庚烷等具有独特药代动力学性能的化合物，用于治疗“急性大麻素过量”。
• [EN] NOVEL COMPOUNDS FOR TREATING FIBROSIS AND INFLAMMATORY CONDITIONS<br/>[FR] NOUVEAUX COMPOSÉS DE TRAITEMENT DE LA FIBROSE ET D'ÉTATS INFLAMMATOIRES
  申请人：MAKSCIENTIFIC LLC

  公开号：WO2022026478A1

  公开（公告）日：2022-02-03

  Several biological targets have been implicated in the pathogenesis of lung, liver, renal and prostrate fibrotic proliferative diseases. While cannabinoid receptor-mediated signaling has emerged as a novel signaling pathway regulating fibrogenesis and inflammation, the present invention relates generally to biologically active compounds capable of interacting with one or more biological targets including the CB1 and/or the CB2 cannabinoid receptors, and comprise of neutral antagonists, neutral-peripheral antagonists, peripheral antagonists/inverse-agonists, compounds with mixed properties including CB1 antagonist/CB2 agonist properties, and allosteric properties for treating fibrosis of the liver, lung, kidney and the prostrate, and inflammatory conditions, including benign prostatic hyperplasia. Also, aspects of the invention are concerned with imidazoles, triazoles, thiazoles, oxazoles, pyrazoles and dihydropyrazoles containing the 4-(λ2-azaneyl)thiomorpholine 1,1-dioxide group or the 4 λ2-thiomorpholine 1,1-dioxide group.

  肺、肝、肾和前列腺纤维增生性疾病的发病机制涉及多个生物靶点。尽管大麻素受体介导的信号通路已成为调节纤维化和炎症的新型信号通路，但本发明通常涉及与CB1和/或CB2大麻素受体之一或多个生物靶点相互作用的生物活性化合物，包括中性拮抗剂、中性周围拮抗剂、周围拮抗剂/反激动剂、具有混合性质的化合物，包括CB1拮抗剂/CB2激动剂性质和用于治疗肝、肺、肾和前列腺纤维化以及炎症状况，包括良性前列腺增生的变构性。此外，本发明涉及含有4-(λ2-氨基)硫代吗啉1,1-二氧化物基团或4-λ2-硫代吗啉1,1-二氧化物基团的咪唑、三唑、噻唑、噁唑、吡唑和二氢吡唑的方面。
• Branched polyalkylene glycols
  申请人：——

  公开号：US20030219404A1

  公开（公告）日：2003-11-27

  The present invention provides branched polyalkylene glycols useful as a chemically modifying agent for physiologically active polypeptides, wherein two single-chain polyalkylene glycols are linked to a group having a cyclic structure other than a plane structure, and wherein a group having reactivity with an amino acid side chain, an N-terminal amino group or a C-terminal carboxyl group in a polypeptide or a group convertible into the group having reactivity is linked to the group having a structure other than a plane structure.

  本发明提供了分支聚合物烷基乙二醇，用作生理活性多肽的化学修饰剂，其中两个单链聚合物烷基乙二醇连接到一个具有环状结构而非平面结构的基团上，并且将与多肽中的氨基酸侧链、N-末端氨基或C-末端羧基具有反应性的基团或可转化为具有反应性基团的基团连接到具有非平面结构的基团上。