1-bromo-7-(4-chlorophenoxy)-heptane

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-bromo-7-(4-chlorophenoxy)-heptane
• 英文别名: 1-((7-bromoheptyl)oxy)-4-chlorobenzene；1-Bromo-7-(4-chlorophenoxy)heptane；1-(7-bromoheptoxy)-4-chlorobenzene
• 化学式: C₁₃H₁₈BrClO
• 分子量: 305.642
• InChiKey: UGDXYQZUHNDYNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-bromo-7-(4-chlorophenoxy)-heptane 在 苄基三乙基氯化铵 、 sodium acetate 、 potassium carbonate 、 溶剂黄146 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 3.0h， 生成 (Z)-2-(3-(7-(4-chlorophenoxy)heptyloxy)benzylidene)-6,7-dihydro-2H-imidazo[2,1-b][1,3]thiazin-3(5H)-one
  参考文献：
  名称：

  咪唑并噻嗪酮和类似物作为大麻素激活的孤儿G蛋白偶联受体GPR18的拮抗剂的结构活性关系

  摘要：

  GPR18是一种大麻素激活的孤儿G蛋白偶联受体（GPCR），在免疫细胞上选择性表达。尽管其作为炎性疾病和癌症免疫疗法的药物靶标具有巨大潜力，但迄今为止仅描述了极少的GPR18配体。在本研究中，我们研究了（Z）-2-（3-（4-氯苄氧基）亚苄基）-6,7-二氢-2 H-咪唑并[2,1-b] [ 1,3]噻嗪-3（5 ħ） -酮（PSB-CB5，5），是迄今为止描述的最有效的GPR18拮抗剂。合成的类似物表现出对杂环核心的广泛修饰和/或在亚苄基部分的取代基的变化。在β-arrestin募集试验中研究了这些化合物作为四氢大麻酚（THC）激活人GPR18的抑制剂。评估了针对大麻素受体（CB 1和CB 2）和针对GPR55（与大麻素相互作用的另一种孤儿GPCR）的选择性。具有长烷基链（最佳长度：六亚甲基）的苯氧基烷氧基取代的亚苄基亚嗪酮有效地封闭了GPR18，具有与铅结构5相似的高效力。（Z）-2-

  DOI：

  10.1016/j.ejmech.2018.05.050
• 作为产物：
  描述：

  1,7-二溴庚烷 、 对氯苯酚 在 sodium n-propoxide 作用下， 以 丙醇 为溶剂， 反应 6.25h， 生成 1-bromo-7-(4-chlorophenoxy)-heptane
  参考文献：
  名称：

  咪唑并噻嗪酮和类似物作为大麻素激活的孤儿G蛋白偶联受体GPR18的拮抗剂的结构活性关系

  摘要：

  GPR18是一种大麻素激活的孤儿G蛋白偶联受体（GPCR），在免疫细胞上选择性表达。尽管其作为炎性疾病和癌症免疫疗法的药物靶标具有巨大潜力，但迄今为止仅描述了极少的GPR18配体。在本研究中，我们研究了（Z）-2-（3-（4-氯苄氧基）亚苄基）-6,7-二氢-2 H-咪唑并[2,1-b] [ 1,3]噻嗪-3（5 ħ） -酮（PSB-CB5，5），是迄今为止描述的最有效的GPR18拮抗剂。合成的类似物表现出对杂环核心的广泛修饰和/或在亚苄基部分的取代基的变化。在β-arrestin募集试验中研究了这些化合物作为四氢大麻酚（THC）激活人GPR18的抑制剂。评估了针对大麻素受体（CB 1和CB 2）和针对GPR55（与大麻素相互作用的另一种孤儿GPCR）的选择性。具有长烷基链（最佳长度：六亚甲基）的苯氧基烷氧基取代的亚苄基亚嗪酮有效地封闭了GPR18，具有与铅结构5相似的高效力。（Z）-2-

  DOI：

  10.1016/j.ejmech.2018.05.050

文献信息

• Imidazolidinone compounds
  申请人：——

  公开号：US20030087936A1

  公开（公告）日：2003-05-08

  A compound having the formula: 1 in which R 1 , R 2 , R 3 , T, W, m, x, and y are defined as in the specification. Also disclosed is a method of treating enterovirus infection by using a compound described above.

  一个具有以下式子的化合物：1，其中R1、R2、R3、T、W、m、x和y的定义如规范中所述。还公开了一种利用上述化合物治疗肠道病毒感染的方法。
• Certain di-(substituted phenoxy) alkanes and hypolipidaemic use thereof
  申请人：Beecham Group Limited

  公开号：US04154850A1

  公开（公告）日：1979-05-15

  A class of di-(substituted phenoxy) alkanes having from 7 to 25 carbon atoms in the alkane moiety have hypolipidaemic activity.

  一类具有低脂作用的二-(取代苯氧基)烷基，其烷基部分含有7至25个碳原子。
• Guanidines: Synthesis of Novel Histamine H3R Antagonists with Additional Breast Anticancer Activity and Cholinesterases Inhibitory Effect
  作者：Marek Staszewski、Magdalena Iwan、Tobias Werner、Marek Bajda、Justyna Godyń、Gniewomir Latacz、Agnieszka Korga-Plewko、Joanna Kubik、Natalia Szałaj、Holger Stark、Barbara Malawska、Anna Więckowska、Krzysztof Walczyński

  DOI：10.3390/ph16050675

  日期：——

  This study examines the properties of novel guanidines, designed and synthesized as histamine H3R antagonists/inverse agonists with additional pharmacological targets. We evaluated their potential against two targets viz., inhibition of MDA-MB-231, and MCF-7 breast cancer cells viability and inhibition of AChE/BuChE. ADS10310 showed micromolar cytotoxicity against breast cancer cells, combined with nanomolar affinity at hH3R, and may represent a promising target for the development of an alternative method of cancer therapy. Some of the newly synthesized compounds showed moderate inhibition of BuChE in the single-digit micromolar concentration ranges. H3R antagonist with additional AChE/BuChE inhibitory effect might improve cognitive functions in Alzheimer’s disease. For ADS10310, several in vitro ADME-Tox parameters were evaluated and indicated that it is a metabolically stable compound with weak hepatotoxic activity and can be accepted for further studies.

  本研究考察了新型胍类化合物的特性，它们被设计合成为组胺 H3R 拮抗剂/反激动剂，并具有额外的药理靶点。我们评估了它们在抑制 MDA-MB-231 和 MCF-7 乳腺癌细胞活力以及抑制 AChE/BuChE 这两个靶点上的潜力。ADS10310 对乳腺癌细胞具有微摩尔细胞毒性，对 hH3R 具有纳摩尔亲和力，可能是开发癌症治疗替代方法的一个有前途的靶点。一些新合成的化合物在个位数微摩尔浓度范围内对 BuChE 有中度抑制作用。具有额外 AChE/BuChE 抑制作用的 H3R 拮抗剂可能会改善阿尔茨海默氏症患者的认知功能。对 ADS10310 的几个体外 ADME-Tox 参数进行了评估，结果表明它是一种代谢稳定的化合物，具有较弱的肝毒性活性，可以接受进一步研究。
• Design, Synthesis, and Structure−Activity Relationship of Pyridyl Imidazolidinones:  A Novel Class of Potent and Selective Human Enterovirus 71 Inhibitors
  作者：Kak-Shan Shia、Wen-Tai Li、Chung-Ming Chang、Ming-Chu Hsu、Jyh-Haur Chern、Max K. Leong、Sung-Nien Tseng、Chung-Chi Lee、Yen-Chun Lee、Shu-Jen Chen、Kuan-Chang Peng、Huan-Yi Tseng、Yi-Ling Chang、Chia-Liang Tai、Shin-Ru Shih

  DOI：10.1021/jm010536a

  日期：2002.4.1

  When skeletons of Win compounds were used as templates, computer-assisted drug design led to the identification of a novel series of imidazolidinone derivatives with significant antiviral activity against enterovirus 71(EV 71), the infection of which had resulted in about 80 fatalities during the 1998 epidemic outbreak in Taiwan. In addition to inhibiting all the genotypes (A, B, and C) of EV 71 in the submicromolar to low micromolar range, compounds 1 and 8 were extensively evaluated against a variety of viruses, showing potent activity against coxsackievirus A9 (IC50 = 0.47-0.55 muM) and coxsackievirus A24 (IC50 = 0.47-0.55 muM) as well as moderate activity against enterovirus 68 (IC50 = 2.13 muM) and echovirus 9 (IC50 = 2.6 muM). Our SAR studies revealed that imidazolidinone analogues with an aryl substituent at the para position of the phenoxyl ring, such as compounds 20, 21, 27, 57, 58, and 61, in general exhibited the highest activity against EV 71. Among them, compound 20 and its corresponding hydrochloride salt 57, in terms of potency and selectivity index, appear to be the most promising candidates in this series for further development of anti-EV-71 agents. Preliminary results of the study on the mode of action by a time-course experiment suggest that test compounds 1 and 8 can effectively inhibit the virus replication at the early stages, referring to virus attachment or uncoating. This indicates that the surface protein may be the target for this type of compounds.
• Chlorophenoxy aminoalkyl derivatives as histamine H3R ligands and antiseizure agents
  作者：Kamil Kuder、Dorota Łażewska、Gniewomir Latacz、Johannes Stephan Schwed、Tadeusz Karcz、Holger Stark、Janina Karolak-Wojciechowska、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bmc.2015.11.021

  日期：2016.1

  A series of twenty new chlorophenoxyalkylamine derivatives (9-28) was synthesized and evaluated on their binding properties at the human histamine H-3 receptor (hH(3)R). The spacer alkyl chain contained five to seven carbon atoms. The highest affinities have shown the 4-chloro substituted derivatives 10 and 25 (K-i = 133 and 128 nM, respectively) classified as antagonists in cAMP accumulation assay (EC50 = 72 and 75 nM, respectively). Synthesized compounds were also evaluated for anticonvulsant activity in Antiepileptic Screening Program (ASP) at National Institute of Neurological Disorders and Stroke (USA). Two compounds (4-chloro substituted derivatives: 20 and 26) were the most promising and showed in the MES seizure model in rats (after ip administration) ED50 values of 14 mg/kg and 13.18 mg/kg, respectively. Protective indexes (PI = TD50/ED50) were 3.2 for 20 and 3.8 for 26. Moreover, molecular modeling and docking studies were undertaken to explain affinity at hH(3)R of target compounds, and the experimentally and in silico estimation of properties like lipophilicity and metabolism was performed. Antiproliferative effects have been also investigated in vitro for selected compounds (10 and 25). These compounds neither possessed significant antiproliferative and antitumor activity, nor modulated CYP3A4 activity up to concentration of 10 mu M. (C) 2015 Published by Elsevier Ltd.