Xiaohan Liu, Bin Zhou, Yan Chen, Jinyuan Lin, Chenwen Shao, Liuzeng Chen, Banfeng Ruan, Xingxing Zhang, Yong Qian
{"title":"用于治疗阿尔茨海默病的17β-HSD10抑制剂2-苯基- 1h -苯并咪唑衍生物的设计与合成","authors":"Xiaohan Liu, Bin Zhou, Yan Chen, Jinyuan Lin, Chenwen Shao, Liuzeng Chen, Banfeng Ruan, Xingxing Zhang, Yong Qian","doi":"10.1039/d4md00861h","DOIUrl":null,"url":null,"abstract":"<p><p>It has been reported that 17β-HSD10 plays a key role in Alzheimer's disease. Here, a total of 44 2-phenyl-1<i>H</i>-benzo[<i>d</i>]imidazole derivatives were designed and synthesized as novel 17β-HSD10 inhibitors based on rational design and SAR studies. Among them, compound 33 (<i>N</i>-(4-(1,4,6-trimethyl-1<i>H</i>-benzo[<i>d</i>] imidazol-2-yl)phenyl)cyclohexanecarboxamide) showed high inhibitory efficacy (17β-HSD10 IC<sub>50</sub> = 1.65 ± 0.55 μM) and low toxicity (HepaRG IC<sub>50</sub> >100 μM). The Morris water maze experiment revealed that compound 33 could alleviate cognitive impairment induced by scopolamine in mice. This study facilitates the further development of more potent 17β-HSD10 inhibitors for the treatment of Alzheimer's disease.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1000,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947984/pdf/","citationCount":"0","resultStr":"{\"title\":\"Design and synthesis of 2-phenyl-1<i>H</i>-benzo[<i>d</i>]imidazole derivatives as 17β-HSD10 inhibitors for the treatment of Alzheimer's disease.\",\"authors\":\"Xiaohan Liu, Bin Zhou, Yan Chen, Jinyuan Lin, Chenwen Shao, Liuzeng Chen, Banfeng Ruan, Xingxing Zhang, Yong Qian\",\"doi\":\"10.1039/d4md00861h\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>It has been reported that 17β-HSD10 plays a key role in Alzheimer's disease. Here, a total of 44 2-phenyl-1<i>H</i>-benzo[<i>d</i>]imidazole derivatives were designed and synthesized as novel 17β-HSD10 inhibitors based on rational design and SAR studies. Among them, compound 33 (<i>N</i>-(4-(1,4,6-trimethyl-1<i>H</i>-benzo[<i>d</i>] imidazol-2-yl)phenyl)cyclohexanecarboxamide) showed high inhibitory efficacy (17β-HSD10 IC<sub>50</sub> = 1.65 ± 0.55 μM) and low toxicity (HepaRG IC<sub>50</sub> >100 μM). The Morris water maze experiment revealed that compound 33 could alleviate cognitive impairment induced by scopolamine in mice. This study facilitates the further development of more potent 17β-HSD10 inhibitors for the treatment of Alzheimer's disease.</p>\",\"PeriodicalId\":21462,\"journal\":{\"name\":\"RSC medicinal chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-02-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947984/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"RSC medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1039/d4md00861h\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"RSC medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1039/d4md00861h","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Design and synthesis of 2-phenyl-1H-benzo[d]imidazole derivatives as 17β-HSD10 inhibitors for the treatment of Alzheimer's disease.
It has been reported that 17β-HSD10 plays a key role in Alzheimer's disease. Here, a total of 44 2-phenyl-1H-benzo[d]imidazole derivatives were designed and synthesized as novel 17β-HSD10 inhibitors based on rational design and SAR studies. Among them, compound 33 (N-(4-(1,4,6-trimethyl-1H-benzo[d] imidazol-2-yl)phenyl)cyclohexanecarboxamide) showed high inhibitory efficacy (17β-HSD10 IC50 = 1.65 ± 0.55 μM) and low toxicity (HepaRG IC50 >100 μM). The Morris water maze experiment revealed that compound 33 could alleviate cognitive impairment induced by scopolamine in mice. This study facilitates the further development of more potent 17β-HSD10 inhibitors for the treatment of Alzheimer's disease.
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