{"title":"新型氨基苯亚甲基咪唑酮 5-HT2A 受体拮抗剂的合成与体外评估","authors":"Gregory E. Dwulet","doi":"10.1039/D4MD00262H","DOIUrl":null,"url":null,"abstract":"<p >Many drugs target the serotonin 2A (5-HT<small><sub>2A</sub></small>) receptor, including psychedelics, antidepressants, and antipsychotics. This study investigates the 5-HT<small><sub>2A</sub></small> receptor-binding properties of a series of novel compounds with an amino-phenylmethylene-imidazolone (APMI) core structure. Two compounds (<strong>2a</strong> and <strong>2c</strong>) demonstrated significant 5-HT<small><sub>2A</sub></small> receptor-binding affinity without agonistic activity, instead displaying antagonistic effects. Structurally, these compounds differ from previously reported phenethylamine-based antagonists. This work introduces APMIs as a novel pharmacophore for 5-HT<small><sub>2A</sub></small> receptor interaction and provides a foundation for developing new 5-HT<small><sub>2A</sub></small> receptor-targeting therapeutic agents.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and in vitro evaluation of novel amino-phenylmethylene-imidazolone 5-HT2A receptor antagonists†\",\"authors\":\"Gregory E. Dwulet\",\"doi\":\"10.1039/D4MD00262H\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Many drugs target the serotonin 2A (5-HT<small><sub>2A</sub></small>) receptor, including psychedelics, antidepressants, and antipsychotics. This study investigates the 5-HT<small><sub>2A</sub></small> receptor-binding properties of a series of novel compounds with an amino-phenylmethylene-imidazolone (APMI) core structure. Two compounds (<strong>2a</strong> and <strong>2c</strong>) demonstrated significant 5-HT<small><sub>2A</sub></small> receptor-binding affinity without agonistic activity, instead displaying antagonistic effects. Structurally, these compounds differ from previously reported phenethylamine-based antagonists. This work introduces APMIs as a novel pharmacophore for 5-HT<small><sub>2A</sub></small> receptor interaction and provides a foundation for developing new 5-HT<small><sub>2A</sub></small> receptor-targeting therapeutic agents.</p>\",\"PeriodicalId\":21462,\"journal\":{\"name\":\"RSC medicinal chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-06-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"RSC medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/md/d4md00262h\",\"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://pubs.rsc.org/en/content/articlelanding/2024/md/d4md00262h","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Synthesis and in vitro evaluation of novel amino-phenylmethylene-imidazolone 5-HT2A receptor antagonists†
Many drugs target the serotonin 2A (5-HT2A) receptor, including psychedelics, antidepressants, and antipsychotics. This study investigates the 5-HT2A receptor-binding properties of a series of novel compounds with an amino-phenylmethylene-imidazolone (APMI) core structure. Two compounds (2a and 2c) demonstrated significant 5-HT2A receptor-binding affinity without agonistic activity, instead displaying antagonistic effects. Structurally, these compounds differ from previously reported phenethylamine-based antagonists. This work introduces APMIs as a novel pharmacophore for 5-HT2A receptor interaction and provides a foundation for developing new 5-HT2A receptor-targeting therapeutic agents.