3-methyl-2-oxa-1-adamantantanol | 6465-33-4

• 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: 3-methyl-2-oxa-1-adamantantanol
• 英文别名: 3-methyl-2-oxa-1-adamantanol；3-methyl-2-oxatricyclo[3.3.1.13,7]decan-1-ol
• CAS: 6465-33-4
• 化学式: C₁₀H₁₆O₂
• 分子量: 168.236
• InChiKey: ZUGMXCUKQRCVGP-UHFFFAOYSA-N

物化性质

• 沸点：
  257.0±8.0 °C(Predicted)
• 密度：
  1.228±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 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：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-methyl-2-oxa-1-adamantantanol 在 aluminum (III) chloride 、 二乙胺 、 三乙胺 、 potassium hydroxide 作用下， 以 二氯甲烷 、 二甲基亚砜 、 1,2-二氯乙烷 、 异丙醇 为溶剂， 反应 75.0h， 生成 (-)-(7S,11S)-3-chloro-12-[(3-{4-[(5,6-dimethoxyindan-2-yl)methyl]piperidin-1-yl}propyl)amino]-6,7,10,11-tetrahydro-9-methyl-7,11-methanocycloocta[b]quinoline
  参考文献：
  名称：

  一种新型多靶点抗阿尔茨海默氏症化合物的多重合成和体内药效研究

  摘要：

  我们描述了多奈哌齐-海普林杂种的多克合成和体内功效研究，该杂种已被发现在治疗阿尔茨海默病 (AD) 方面显示出有前景的体外多靶点谱。其合成的关键步骤是通过手性 HPLC 对中间体外消旋 Huprine Y 进行新型多克制备型色谱分离。将这种化合物施用于表达人 Aβ42 的转基因 CL4176 和 CL2006 秀丽隐杆线虫菌株，这里用作 AD 的简化动物模型，导致显着保护免受 Aβ42 诱导的毒性。然而，在 CL2006 蠕虫中，这种保护作用并没有伴随着淀粉样蛋白沉积物的减少。对转基因 APPSL 小鼠（一种成熟的 AD 动物模型）口服给药 3 个月，可改善短期记忆，但没有改变 Aβ 肽的大脑水平，也没有改变皮质和海马淀粉样斑块的负荷。尽管 AVCRI104P4 具有明显的保护和认知作用，但与较高的抗胆碱酯酶活性相比，体内 Aβ 降低作用的缺乏可能与其体外对 Aβ 聚集和形成的效力较低有关

  DOI：

  10.3390/molecules20034492
• 作为产物：
  描述：

  3-methyl-2-oxa-1-adamantantanyl methanesulfonate 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 乙基苯 为溶剂， 反应 5.0h， 以94%的产率得到3-methyl-2-oxa-1-adamantantanol
  参考文献：
  名称：

  Enantioselective synthesis of tacrine–huperzine A hybrids. Preparative chiral MPLC separation of their racemic mixtures and absolute configuration assignments by X-ray diffraction analysis

  摘要：

  A new synthesis of racemic 7-substituted bicyclo[3.3.1]non-6-en-3-ones, rac-4, whose key-step involves the reaction of a vinyl triflate, rac-7, with an organometallic reagent, has been developed. This procedure has been applied to the enantioselective synthesis of (+)- and (-)-7-ethylbicyclo[3.3.1]non-6-en-3-one, (+)- and (-)-4b, from which both enantiomers of the cholinesterase inhibitor, tacrine-huperzine A hybrid, 9b, have been obtained. Rac-9b and its related compounds rac-9a and rac-10a were separated into their enantiomers on a preparative scale by medium pressure liquid chromatography (MPLC) using microcrystalline cellulose triacetate as the chiral stationary phase. X-ray diffraction analysis of (-)-10a as the o-iodobenzoic acid salt, allowed us to establish its absolute configuration and deduce those of other enantiopure tacrine-huperzine A hybrids. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(98)00029-9

文献信息

• Synthesis, in Vitro Pharmacology, and Molecular Modeling of Very Potent Tacrine−Huperzine A Hybrids as Acetylcholinesterase Inhibitors of Potential Interest for the Treatment of Alzheimer's Disease
  作者：Pelayo Camps、Rachid El Achab、Diana Marina Görbig、Jordi Morral、Diego Muñoz-Torrero、Albert Badia、Josep Eladi Baños、Nuria María Vivas、Xavier Barril、Modesto Orozco、Francisco Javier Luque

  DOI：10.1021/jm980620z

  日期：1999.8.1

  obtained for the 9-ethyl derivative rac-20, previously prepared by our group. More bulky substituents at position 9 led to less active compounds, although some of them [9-isopropyl (rac-22), 9-allyl (rac-23), and 9-phenyl (rac-26)] show activities similar to that of THA. Substitution at position 1 or 3 with methyl or fluorine atoms always led to more active compounds. Among them, the highest activity

  已合成11种新的12-氨基-6,7,10,11-四氢-7，11-甲基环辛基[b]喹啉衍生物[他克林（THA）-石杉碱A杂种，rac-21-31]作为外消旋混合物并进行了测试作为乙酰胆碱酯酶（AChE）抑制剂。对于苯环上未取代的衍生物，我们小组先前制备的9-乙基衍生物rac-20的活性最高。第9位的更大取代基导致活性较低的化合物，尽管其中某些化合物[9-异丙基（rac-22），9-烯丙基（rac-23）和9-苯基（rac-26）]表现出相似的活性THA。在位置1或3处被甲基或氟原子取代通常会导致活性更高的化合物。其中，对3-氟-9-甲基衍生物rac-28观察到最高的活性[比THA高约15倍，比（-）-石杉碱A高约9倍]。一些THA-石杉碱甲杂化物（rac-19，rac-20，rac-28和rac-30）的活性，通过使用微晶纤维素三乙酸酯通过手性中压液相色谱（手性MPLC）将其分离为对映体作为
• Easy synthesis of 7-alkylbicyclo[3.3.1]non-6-en-3-ones by silica gel-promoted fragmentation of 3-alkyl-2-oxaadamant-1-yl mesylates
  作者：Pelayo Camps、Rachid El Achab、Merce` Font-Bardia、Diana Go¨rbig、Jordi Morral、Diego Mun˜oz-Torrero、Xavier Solans、Montserrat Simon

  DOI：10.1016/0040-4020(96)00217-7

  日期：1996.4

  A synthesis of 7-alkylbicyclo[3.3.1]non-6-en-3-ones4b-f and 4j, k by reaction of the corresponding 3-alkyl-2-oxaadamant-1-yl mesylates3 with silica gel in methylene chloride at room temperature, is described. The method failed to give enones4a, g and the related compounds4l, m, what can be rationalized on mechanistic grounds.

  通过使相应的3-烷基-2-氧杂芳基-1-基甲磺酸基酯3与硅胶在亚甲基中的反应，合成7-烷基双环[3.3.1] non-6-en-3-ones 4b-f和4j，k描述了室温下的氯化物。该方法未能给出烯酮4a，g和相关化合物4l，m，可以根据机械原理对其进行合理化。
• Palladium-Catalyzed Preparation of N-Alkylated Tacrine and Huprine Compounds
  作者：Cyril Ronco、Ludovic Jean、Hakim Outaabout、Pierre-Yves Renard

  DOI：10.1002/ejoc.201001158

  日期：2011.1

  An efficient preparation of N-alkylated tacrine and huprine compounds using palladium-catalyzed amination was developed. Cross-coupling reactions with chloroquinolines and primary amines were achieved in good to excellent yields (50-95 %) following microwave irradiation. This method was found particularly useful for functionalized substrates which undergo degradation under S N Ar conditions and for

  开发了一种使用钯催化胺化的 N-烷基化他克林和胡普林化合物的有效制备方法。微波辐射后，氯喹啉和伯胺的交叉偶联反应以良好到极好的产率（50-95%）实现。发现该方法特别适用于在 SN Ar 条件下发生降解的功能化底物，以及合成基于他克林和胡普林的异二聚体抑制剂，描述了其实例。
• Apoptosis inducing adamantyl derivatives and their usage as anti-cancer
  申请人：Galderma Research & Development, S.N.C.

  公开号：US06127415A1

  公开（公告）日：2000-10-03

  The present invention relates to specific adamantyl or adamantyl group derivative containing retinoid compounds induce apoptosis of cancer cells. These adamantyl retinoid derivatives are useful for the treatment of many cancers and solid tumors, especially androgen-independent prostate cancer, skin cancer, pancreatic carcinomas, colon cancer, melanoma, ovarian cancer, liver cancer, small cell lung carcinoma, non-small cell lung carcinoma, cervical carcinoma, brain cancer, bladder cancer, breast cancer, neuroblastoma/glioblastoma, and leukemia. Also, the invention relates to novel adamantyl or adamantyl group derivative compounds which are useful as active agents for the treatment or prevention of keratinization disorders and other dermatological conditions, and other diseases.

  本发明涉及含有特定金刚烷基或金刚烷基衍生物的视黄醇类化合物，可诱导癌细胞凋亡。这些金刚烷基视黄醇衍生物对许多癌症和实体瘤的治疗有用，特别是雄激素非依赖性前列腺癌、皮肤癌、胰腺癌、结肠癌、黑色素瘤、卵巢癌、肝癌、小细胞肺癌、非小细胞肺癌、宫颈癌、脑癌、膀胱癌、乳腺癌、神经母细胞瘤/胶质母细胞瘤和白血病。此外，本发明还涉及新型金刚烷基或金刚烷基衍生物化合物，其用作治疗或预防角化病和其他皮肤病以及其他疾病的活性剂。
• Apoptosis inducing adamantyl derivatives and their usage as anti-cancer agents, especially for cervical cancers and dysplasias
  申请人：Galderma Research & Development S.N.C.

  公开号：US06462064B1

  公开（公告）日：2002-10-08

  The invention relates to the discovery that specific adamantyl or adamantyl group derivatives containing retinoid-related compounds induce apoptosis of cancer cells and therefore may be used for the treatment of cancer, including advanced cancer. Also, the present invention relates to novel adamantyl or adamantyl group derivatives containing retinoid compounds and their usage for treatment and/or prevention of cancer, keratinization disorders, dermatological conditions, and other therapies More specifically, it has been shown that such adamantyl compounds, e.g., 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid, 2-[3-(1-adamantyl)-4-methoxyphenyl]-5-benzimidazole carboxylic acid, and 6-[3-(1-adamantyl)-4,5-methylenedioxyphenyl]-2-naphthoic acid, can be used to treat or prevent cervical cancers and precancers such as cervical dysplasias, including high grade and low grade dysplasias.

  该发明涉及到发现含有类视黄醇相关化合物的特定金刚烷基或金刚烷基衍生物诱导癌细胞凋亡，并因此可用于治疗包括晚期癌症在内的癌症。此外，本发明涉及到新型含有类视黄醇化合物的金刚烷基或金刚烷基衍生物及其用于治疗和/或预防癌症、角化障碍、皮肤病和其他治疗方案的用途。更具体地，已经证明这种金刚烷基化合物，例如6-[3-(1-金刚烷基)-4-甲氧基苯基]-2-萘酸、2-[3-(1-金刚烷基)-4-甲氧基苯基]-5-苯并咪唑羧酸和6-[3-(1-金刚烷基)-4,5-亚甲二氧基苯基]-2-萘酸，可用于治疗或预防宫颈癌和宫颈上皮内瘤变，包括高度和低度上皮内瘤变。