1-{2’-[(5''-bromopentyl)oxy]ethyl}-4-methoxybenzene

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 1-{2’-[(5''-bromopentyl)oxy]ethyl}-4-methoxybenzene
• 英文别名: 1-[2-[(5-Bromopentyl)oxy]ethyl]-4-methoxybenzene；1-[2-(5-bromopentoxy)ethyl]-4-methoxybenzene
• 化学式: C₁₄H₂₁BrO₂
• 分子量: 301.224
• InChiKey: UIWQJNXSBLWQPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-胺-1,2,3,4-四氢盐酸氯酯 、 1-{2’-[(5''-bromopentyl)oxy]ethyl}-4-methoxybenzene 在 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以52%的产率得到N-[5'-(4''-methoxyphenethyloxy)pentyl]-1,2,3,4-tetrahydroacridin-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：

  1,5-二溴戊烷 、 对甲氧基苯乙醇 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以73%的产率得到1-{2’-[(5''-bromopentyl)oxy]ethyl}-4-methoxybenzene
  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

• 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。
• Dichloroaniline derivatives
  申请人：Glaxo Group Limited

  公开号：US04943591A1

  公开（公告）日：1990-07-24

  The invention provides compounds of the general formula (I) ##STR1## wherein X represents a C.sub.1-6 alkylene, C.sub.2-6 alkenylene or C.sub.2-6 alkynylene chain and Y represents a bond, or a C.sub.1-4 alkylene, C.sub.2-4 alkenylene or C.sub.2-4 alkynylene chain with the proviso that the sum total of carbon atoms in X and Y is not more than 8; Ar represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms or the groups C.sub.1-3 alkyl, nitro, --(CH.sub.2).sub.q R [where R is hydroxy, C.sub.1-3 alkoxy, --NR.sup.3 R.sup.4 (where R.sup.3 and R.sup.4 each represent a hydrogen atom, or a C.sub.1-4 alkyl group, or --NR.sup.3 R.sup.4 forms a saturated heterocyclic amino group which has 5-7 ring members and optionally contains in the ring one or more atoms selected from --O-- or --S-- or a group --NH-- or --N(CH.sub.3)--), --NR.sup.5 COR.sup.6 (where R.sup.5 represents a hydrogen atom or a C.sub.1-4 alkyl group, and R.sup.6 represents a hydrogen atom or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy or --NR.sup.3 R.sup.4 group), and q represents an integer from 0 to 3], --NR.sup.5 COR.sup.19 (where R.sup.5 is as defined above and R.sup.19 represents a phenyl group), --(CH.sub.2).sub.r R.sup.7 [where R.sup.7 represents --NR.sup.5 SO.sub.2 R.sup.8 (where R.sup.8 represents a C.sub.1-4 alkyl, phenyl or --NR.sup.3 R.sup.4 group), --NR.sup.5 COCH.sub.2 N(R.sup.5).sub.2 (where each of the groups R.sup.5 represents a hydrogen atom or a C.sub.1-4 alkyl group), --COR.sup.9 (where R.sup.9 represents hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4), --SR.sup.10 (where R.sup.10 is a hydrogen atom, or a C.sub.1-4 alkyl group optionally substituted by hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4), --SOR.sup.10, --SO.sub.2 R.sup.10, --CN, or --NR.sup.11 R.sup.12 (where R.sup.11 and R.sup.12 represent a hydrogen atom or a C.sub.1-4 alkyl group, at least one of which is C.sub.2-4 alkyl substituted by a hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4), and r represents an integer from 0 to 3], --O(CH.sub.2).sub.q COR.sup.9 (where q and R.sup.9 are as defined above), or --O(CH.sub.2).sub.t R.sup.13 [where R.sup.13 represents hydroxy, NR.sup.3 R.sup.4, NR.sup.11 R.sup.12 or a C.sub.1-4 alkoxy group optionally substituted by hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4, and t is an integer 2 or 3], or Ar is a phenyl group substituted by an alkylenedioxy group --O(CH.sub.2).sub.p O-- where p is 1 or 2; R.sup.1 and R.sup.2 each represents a hydrogen atom or a C.sub.1-3 alkyl group, with the proviso that the sum total of carbon atoms in R.sup.1 and R.sup.2 is not more than 4; and physiologically acceptable salts and solvates (e.g. hydrates) thereof. The compounds of formula (I) have a stimulant action at .beta..sub.2 -adrenoreceptors and are useful, in particular, in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.

  本发明提供了一般式(I)的化合物：##STR1## 其中，X代表C.sub.1-6烷基，C.sub.2-6烯基或C.sub.2-6炔基链，Y代表键或C.sub.1-4烷基，C.sub.2-4烯基或C.sub.2-4炔基链，但X和Y中碳原子的总和不超过8；Ar代表苯基，可选地由一个或多个取代基选自卤素原子或C.sub.1-3烷基，硝基，--(CH.sub.2).sub.qR [其中R为羟基，C.sub.1-3烷氧基，--NR.sup.3R.sup.4（其中R.sup.3和R.sup.4各代表氢原子或C.sub.1-4烷基，或--NR.sup.3R.sup.4形成有5-7个环成员的饱和杂环氨基，其中环中可选地包含一个或多个原子选自--O--或--S--或--NH--或--N(CH.sub.3)--），--NR.sup.5COR.sup.6（其中R.sup.5代表氢原子或C.sub.1-4烷基，R.sup.6代表氢原子或C.sub.1-4烷基，C.sub.1-4烷氧基或--NR.sup.3R.sup.4基），q代表0至3的整数]，--NR.sup.5COR.sup.19（其中R.sup.5如上定义，R.sup.19代表苯基），--(CH.sub.2).sub.rR.sup.7 [其中R.sup.7代表--NR.sup.5SO.sub.2R.sup.8（其中R.sup.8代表C.sub.1-4烷基，苯基或--NR.sup.3R.sup.4基），--NR.sup.5COCH.sub.2N(R.sup.5).sub.2（其中每个R.sup.5代表氢原子或C.sub.1-4烷基），--COR.sup.9（其中R.sup.9代表羟基，C.sub.1-4烷氧基或NR.sup.3R.sup.4），--SR.sup.10（其中R.sup.10为氢原子或可选地由羟基，C.sub.1-4烷氧基或NR.sup.3R.sup.4取代的C.sub.1-4烷基），--SOR.sup.10，--SO.sub.2R.sup.10，--CN或--NR.sup.11R.sup.12（其中R.sup.11和R.sup.12代表氢原子或C.sub.1-4烷基，至少有一个是由羟基，C.sub.1-4烷氧基或NR.sup.3R.sup.4取代的C.sub.2-4烷基），r代表0至3的整数]，--O(CH.sub.2).sub.qCOR.sup.9（其中q和R.sup.9如上定义），或--O(CH.sub.2).sub.tR.sup.13 [其中R.sup.13代表羟基，NR.sup.3R.sup.4，NR.sup.11R.sup.12或可选地由羟基，C.sub.1-4烷氧基或NR.sup.3R.sup.4取代的C.sub.1-4烷氧基，t为2或3]，或Ar是由烷二氧基基团--O(CH.sub.2).sub.pO-取代的苯基，其中p为1或2；R.sup.1和R.sup.2各代表氢原子或C.sub.1-3烷基，但R.sup.1和R.sup.2中碳原子的总和不超过4；以及其生理上可接受的盐和溶剂（例如水合物）。式(I)的化合物在.beta..sub.2-肾上腺素受体上具有兴奋作用，并且特别适用于治疗与可逆性气道阻塞有关的疾病，如哮喘和慢性支气管炎。
• Dichloroaniline derivatives for the therapy or prophylaxysis of a
  申请人：Glaxo Group Limited

  公开号：US05006556A1

  公开（公告）日：1991-04-09

  The invention provides compounds of the general formula (I) ##STR1## wherein X represents a C.sub.1-6 alkylene, C.sub.2-6 alkenylene or C.sub.2-6 alkynylene chain and Y represents a bond, or a C.sub.1-4 alkylene, C.sub.2-4 alkenylene or C.sub.2-4 alkynylene chain with the proviso that the sum total of carbon atoms in X and Y is not more than 8; Ar represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms or the groups C.sub.1-3 alkyl, nitro, --(CH.sub.2)qR [where R is hydroxy, C.sub.1-3 alkoxy, --NR.sup.3 R.sup.4 (where R.sup.3 and R.sup.4 each represent a hydrogen atom, or a C.sub.1-4 alkyl group, or --NR.sup.3 R.sup.4 forms a saturated heterocyclic amino group which has 5-7 ring members and optionally contains in the ring one or more atoms selected from --O-- or --S-- or a group --NH-- or --N(CH.sub.3)--), --NR.sup.5 COR.sup.6 (where R.sup.5 represents a hydrogen atom or a C.sub.1-4 alkyl group, and R.sup.6 represents a hydrogen atom or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy or --NR.sup.3 R.sup.4 group), and q represents an integer from 0 to 3], --NR.sup.5 COR.sup.19 (where R.sup.5 is as defined above and R.sup.19 represents a phenyl group), --(CH.sub.2).sub.r R.sup.7 [where R.sup.7 represents --NR.sup.5 SO.sub.2 R.sup.8 (where R.sup.8 represents a C.sub.1-4 alkyl, phenyl or --NR.sup.3 R.sup.4 group), --NR.sup.5 COCH.sub.2 N(R.sup.5).sub.2 (where each of the groups R.sup.5 represents a hydrogen atom or a C.sub.1-4 alkyl group), --COR.sup.9 (where R.sup.9 represents hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4), --SR.sup.10 (where R.sup.10 is a hydrogen atom, or a C.sub.1-4 alkyl group optionally substituted by hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4), --SOR.sup.10, --SO.sub.2 R.sup.10, --CN, or --NR.sup.11 R.sup.12 (where R.sup.11 and R.sup.12 represent a hydrogen atom or a C.sub.1-4 alkyl group, at least one of which is C.sub.2-4 alkyl substituted by a hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4 group), and r represents an integer from 0 to 3], --O(CH.sub.2).sub.q COR.sup.9 (where q and R.sup.9 are as defined above), or --O(CH.sub.2).sub.t R.sup.13 [where R.sup.13 represents hydroxy, NR.sup.3 R.sup.4, NR.sup.11 R.sup.12 or a C.sub.1-4 alkoxy group optionally substituted by hydroxy, C.sub.1-4 alkoxy or NR.sup.3 R.sup.4, and t is an integer 2 or 3], or Ar is a phenyl group substituted by an alkylenedioxy group --O(CH.sub.2).sub.p O-- where p is 1 or 2; R.sup.1 and R.sup.2 each represents a hydrogen atom or a C.sub.1-3 alkyl group, with the proviso that the sum total of carbon atoms in R.sup.1 and R.sup.2 is not more than 4; and physiologically acceptable salts and solvates (e.g. hydrates) thereof. The compounds of formula (I) have a stimulant action at .beta..sub.2 -adrenoreceptors and are useful, in particular, in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.

  本发明提供了一般式（I）的化合物：##STR1## 其中X代表C.sub.1-6烷基，C.sub.2-6烯基或C.sub.2-6炔基链，Y代表键或C.sub.1-4烷基，C.sub.2-4烯基或C.sub.2-4炔基链，但X和Y中碳原子的总和不超过8；Ar代表苯基，可选地取代一个或多个取代基，所述取代基选择自卤原子或C.sub.1-3烷基、硝基、--(CH.sub.2)qR [其中R为羟基、C.sub.1-3烷氧基、--NR.sup.3R.sup.4（其中R.sup.3和R.sup.4分别代表氢原子，或C.sub.1-4烷基，或--NR.sup.3R.sup.4形成有5-7个环成员的饱和杂环氨基，可选地在环中包含一个或多个选择自--O--或--S--或--NH--或--N(CH.sub.3)--的原子或基），--NR.sup.5COR.sup.6（其中R.sup.5代表氢原子或C.sub.1-4烷基，R.sup.6代表氢原子或C.sub.1-4烷基、C.sub.1-4烷氧基或--NR.sup.3R.sup.4基），q代表0至3的整数]、--NR.sup.5COR.sup.19（其中R.sup.5如上定义，R.sup.19代表苯基），--(CH.sub.2).sub.rR.sup.7 [其中R.sup.7代表--NR.sup.5SO.sub.2R.sup.8（其中R.sup.8代表C.sub.1-4烷基、苯基或--NR.sup.3R.sup.4基）、--NR.sup.5COCH.sub.2N(R.sup.5).sub.2（其中R.sup.5的每个基代表氢原子或C.sub.1-4烷基）、--COR.sup.9（其中R.sup.9代表羟基、C.sub.1-4烷氧基或NR.sup.3R.sup.4）、--SR.sup.10（其中R.sup.10为氢原子或C.sub.1-4烷基，可选地被羟基、C.sub.1-4烷氧基或NR.sup.3R.sup.4取代）、--SOR.sup.10、--SO.sub.2R.sup.10、--CN或--NR.sup.11R.sup.12（其中R.sup.11和R.sup.12代表氢原子或C.sub.1-4烷基，至少一个基被羟基、C.sub.1-4烷氧基或NR.sup.3R.sup.4取代，且其中至少一个基为C.sub.2-4烷基），r代表0至3的整数]、--O(CH.sub.2).sub.qCOR.sup.9（其中q和R.sup.9如上定义），或--O(CH.sub.2).sub.tR.sup.13 [其中R.sup.13代表羟基、NR.sup.3R.sup.4、NR.sup.11R.sup.12或C.sub.1-4烷氧基，可选地被羟基、C.sub.1-4烷氧基或NR.sup.3R.sup.4取代，t为2或3]，或Ar为取代有烷二氧基基团--O(CH.sub.2).sub.pO-的苯基，其中p为1或2；R.sup.1和R.sup.2各代表氢原子或C.sub.1-3烷基，但R.sup.1和R.sup.2中碳原子的总和不超过4；以及其生理上可接受的盐和溶剂（例如水合物）。式（I）化合物在β.sub.2-肾上腺素受体上具有兴奋作用，特别适用于治疗与可逆气道阻塞相关的疾病，例如哮喘和慢性支气管炎。
• Dichloroaniline Derivatives
  申请人：GLAXO GROUP LIMITED

  公开号：EP0181709A1

  公开（公告）日：1986-05-21

  57 The invention provides compounds of the general formula (I) wherein X represents a C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene chain and Y represents a bond, or a C1-4 alkylene, C2-4 alkenylene of C2-4 alkynylene chain with the proviso that the sum total of carbon atoms in X and Y is not more than 8; Ar represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms, or the groups C1-3 alkyl, C1-3 alkoxy, -(CH2)q OH (where q represents an integer from 0 to 3), - NR3R4 (where R3 and R4 each represents a hydrogen atom, or a C1-4, alkyl group, or NR3R4 forms a saturated heterocyclic amino group which has 5-7 ring members and optionally contains in the ring one or more atoms selected from -O- or -S- or a group -NH- or -N(CH3)-), or -NR5COR6 (where Rs represents a hydrogen atom or a C1-4 alkyl group, and R6 represents a hydrogen atom or a C1-4 alkyl, C1-4 alkoxy, phenyl or -NR3R4 group), or Ar as a phenyl group may be substituted by an alkylenedioxy group of formula -O(CH2)pO-, where p is 1 or 2; R' and R2 each represents a hydrogen atom or a Cl-3 alkyl group, with the proviso that the sum total of carbon atoms in R' and R2 is not more than 4; and physiologically acceptable salts and solvates (e.g. hydrates) thereof. The compounds of formula (1) have a selective stimulent action at β2-adrenoreceptors and are useful, in particular, in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.

  57 本发明提供通式 (I) 的化合物 其中 X 代表 C1-6 亚烷基、C2-6 亚烯基或 C2-6 亚炔基链，以及 Y 代表键，或 C1-4 亚烷基、C2-4 亚烯基或 C2-4 亚炔基链，但 X 和 Y 中的碳原子总数不超过 8；Ar 代表可任选被一个或多个取代基取代的苯基，这些取代基可选自卤素原子、或 C1-3 烷基、C1-3 烷氧基、-(CH2)q OH（其中 q 代表 0 至 3 的整数）、-NR3R4（其中 R3 和 R4 各代表一个氢原子或一个 C1-4 烷基、或 NR3R4 形成饱和杂环氨基，该氨基具有 5-7 个环成员，并可选择在环中包含一个或多个选自 -O- 或 -S- 或基团 -NH- 或 -N(CH3)- 的原子），或 -NR5COR6 （其中 Rs 代表氢原子或 C1-4 烷基、R6代表氢原子或C1-4烷基、C1-4烷氧基、苯基或-NR3R4基团），或Ar作为苯基可被式-O(CH2)pO-的亚烷基二氧基取代，其中p为1或2；R' 和 R2 各代表一个氢原子或一个 Cl-3 烷基，但 R' 和 R2 中的碳原子总数不超过 4 个；以及生理上可接受的盐和溶液（如水合物）。如水合物）。 式（1）化合物对 β2-肾上腺素受体具有选择性刺激作用，特别适用于治疗与可逆性气道阻塞有关的疾病，如哮喘和慢性支气管炎。
• US4943591A
  申请人：——

  公开号：US4943591A

  公开（公告）日：1990-07-24