4-[2'-{(5''-bromopentyl)oxy}ethyl]1,2-dibenzyloxybenzene | 178486-13-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-[2'-{(5''-bromopentyl)oxy}ethyl]1,2-dibenzyloxybenzene
• 英文别名: 5-bromopentyl-2-[3,4-di(phenylmethoxy)phenyl]ethyl-ether；4-[2-(5-Bromopentoxy)ethyl]-1,2-bis(phenylmethoxy)benzene
• CAS: 178486-13-0
• 化学式: C₂₇H₃₁BrO₃
• 分子量: 483.445
• InChiKey: OKHBJKRGGWQAKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  31
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  4-[2'-{(5''-bromopentyl)oxy}ethyl]1,2-dibenzyloxybenzene 在 10 wt% Pd(OH)2 on carbon 、 氢气 、 potassium hydroxide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 N-{5’-[3'',4''-(dihydroxy)phenethyloxy]pentyl}-1,2,3,4-tetrahidroacridin-9-amine
  参考文献：
  名称：

  Tacrine-O-protected phenolics heterodimers as multitarget-directed ligands against Alzheimer's disease: Selective subnanomolar BuChE inhibitors

  摘要：

  Concerned by the devastating effects of Alzheimer's disease, and the lack of effective drugs, we have carried out the design of a series of tacrine-phenolic heterodimers in order to tackle the multifactorial nature of the disease.Hybridization of both pharmacophores involved the modification of the nature (imino, amino, ether) and the length of the tether, together with the type (hydroxy, methoxy, benzyloxy), number and position of the substituents on the aromatic residue. Title compounds were found to be strong and selective inhibitors of human BuChE (from low nanomolar to subnanomolar range), an enzyme that becomes crucial in the more advanced stages of the disease.The lead compound, bearing an ether-type tether, had an IC50 value of 0.52 nM against human BuChE, and a selectivity index of 323, with an 85-fold increase of activity compared to parent tacrine; key interactions were analysed using molecular modelling. Moreover, it also inhibited the self-aggregation of A beta 42, lacking neurotoxicity up to 5 mu M concentration, and showed neuroprotective activity in primary rat neurons in a serum and K+ deprivation model, widely employed for reproducing neuronal injury and senescence. Moreover, low hepatoxicity effects and complete stability under physiological conditions were found for that compound.So, overall, our lead compound can be considered as a promising multitarget-directed ligand against Alzheimer's disease, and a good candidate for developing new drugs. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.07.053
• 作为产物：
  描述：

  氯化苄 在 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 4-[2'-{(5''-bromopentyl)oxy}ethyl]1,2-dibenzyloxybenzene
  参考文献：
  名称：

  直接获得源自 2-芳基乙醇的新型促线粒体药物作为有效和选择性的抗增殖剂

  摘要：

  开发具有改善活性和减少副作用的新型细胞抑制剂以应对癌症的必要性促使我们研究线粒体靶向化合物，这种方法在细胞毒性剂的选择性运输方面受到关注。 我们设想了通过不同长度的烃链将苯乙醇基序与三苯基鏻支架（线粒体导向载体）缀合的可能性，该基序在芳基部分上装饰有一系列基于苯酚的取代基。因此，此类包含苯乙基骨架的化合物可被视为源自橄榄树中发现的相关天然对应物（例如酪醇、羟基酪醇）的掩蔽酚类化合物。 标题化合物对所测试的六种人类肿瘤细胞系表现出非常强的体外抗增殖活性，在大多数情况下，GI 50值范围从纳摩尔（0.026 ± 0.010 μM，对于36）到亚微摩尔范围；与经典化疗药物（如 5-氟尿嘧啶或顺铂）相比，这代表了高达 350 倍的改善。有趣的是，接头长度的减少导致针对非肿瘤细胞的 GI 50值增加，从而显着提高了选择性（SI 高达 269）。 非常有希望的抗增殖活性促使我们进一步研究它们对多药耐药细胞系

  DOI：

  10.1016/j.ejmech.2021.113980

文献信息

• Derivatives of 2-amino-1,2,3,4-tetrahydronaphthalene active on the
  申请人：Zambon Group

  公开号：US05674909A1

  公开（公告）日：1997-10-07

  Compounds of formula ##STR1## wherein R, R', R", R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, X, Y, m, n and p have the meanings reported in the description; and their pharmaceutically acceptable salts are described. The compounds of formula I are useful in the treatment of arterial hypertension and congestive heart failure, of renal failure, of peripheral arteriopathies, of cerebrovascular insufficiencies and of ischemic cardiopathy.

  化学式为##STR1##的化合物，其中R、R'、R"、R₁、R₂、R₃、R₄、R₅、R₆、X、Y、m、n和p的含义如描述中所述；以及它们的药用盐被描述。化合物I的化学式在治疗动脉高血压和充血性心力衰竭、肾功能衰竭、外周动脉病变、脑血管供血不足和缺血性心脏病方面具有用途。
• Tuning the activity of iminosugars: novel <i>N</i>-alkylated deoxynojirimycin derivatives as strong BuChE inhibitors
  作者：Ana I. Ahuja-Casarín、Penélope Merino-Montiel、José Luis Vega-Baez、Sara Montiel-Smith、Miguel X. Fernandes、Irene Lagunes、Inés Maya、José M. Padrón、Óscar López、José G. Fernández-Bolaños

  DOI：10.1080/14756366.2020.1847101

  日期：2021.1.1

  Abstract We have designed unprecedented cholinesterase inhibitors based on 1-deoxynojirimycin as potential anti-Alzheimer’s agents. Compounds are comprised of three key structural motifs: the iminosugar, for interaction with cholinesterase catalytic anionic site (CAS); a hydrocarbon tether with variable lengths, and a fragment derived from 2-phenylethanol for promoting interactions with peripheral

  摘要 我们设计了以1-脱氧野oji霉素为基础的胆碱酯酶抑制剂，这是潜在的抗阿尔茨海默氏病药物。化合物由三个关键的结构基序组成：亚氨基糖，用于与胆碱酯酶催化阴离子位点（CAS）相互作用；具有可变长度的烃系链，以及衍生自2-苯基乙醇的片段，用于促进与周围阴离子位点（PAS）的相互作用。标题化合物对BuChE表现出良好的选择性，这在很大程度上取决于取代模式和系链的长度。发现铅化合物是BuChE的强混合抑制剂（IC 50= 1.8和1.9 µM）。使用分子对接模拟分析了前导化合物的推测结合模式，揭示了与催化位点（His438）和CAS（Trp82和Glu197）的氢键相互作用以及与PAS的范德华相互作用（Thr284，Pro285，Asn289）。它们还缺乏100 µM的抗肿瘤和非肿瘤细胞的显着抗增殖活性，因此它们有望成为通过胆碱能疗法治疗阿尔茨海默氏病的新药。
• DERIVATIVES OF 2-AMINO-1,2,3,4-TETRAHYDRO-NAPHTHALENE ACTIVE ON THE CARDIOVASCULAR SYSTEM
  申请人：ZAMBON GROUP S.p.A.

  公开号：EP0781126B1

  公开（公告）日：2001-12-12
• [EN] DERIVATIVES OF 2-AMINO-1,2,3,4-TETRAHYDRO-NAPHTHALENE ACTIVE ON THE CARDIOVASCULAR SYSTEM<br/>[FR] DERIVES DE 2-AMINO-1,2,3-4-TETRAHYDRONAPHTALENE ACTIFS SUR LE SYSTEME CARDIO-VASCULAIRE
  申请人：——

  公开号：WO1996008228A2

  公开（公告）日：1996-03-21

  [EN] Derivatives of 2-amino-1,2,3,4-tetrahydro-naphtalene according to formula (I) for the treatment of arterial hypertension, congestive heart failure, renal failure, peripheral arteriopathies or cerebro-vascular insufficiencies.
  [FR] Dérivés de 2-amino-1,2,3,4-tétrahydro-naphtalène de la formule (I) destinés au traitement de l'hypertension artérielle, de l'insuffisance cardiaque, de l'insuffisance rénale, des artériopathies périphériques ou des insuffisances vasculaires cérébrales.