{"title":"Structure-Affinity-Pharmacokinetics Relationships of Novel 18F-Labeled 1,4-Diazepane Derivatives for Orexin 1 Receptor Imaging","authors":"Yui Ishizaka, Hiroyuki Watanabe, Masahiro Ono","doi":"10.1021/acs.jmedchem.4c01090","DOIUrl":null,"url":null,"abstract":"The orexin 1 receptor (OX1R) has been suggested to be involved in the reward and autonomic nervous systems. Positron emission tomography (PET) of OX1R contributes to elucidating its role and developing new drugs. However, there are no useful PET probes for in vivo imaging of OX1R. Here, we newly designed and synthesized <sup>18</sup>F-labeled 1,4-diazepane derivatives and evaluated their utilities as OX1R PET probes. In particular, BTF showed high and selective binding affinity for OX1R. In a biodistribution study using normal mice, [<sup>18</sup>F]BTF exhibited brain uptake, and radioactivity in the brain was significantly decreased by preinjection of unlabeled BTF. In a PET/CT study, it was suggested that [<sup>18</sup>F]BTF has the potential to visualize high-expression regions of OX1R in the normal mouse brain. Collectively, [<sup>18</sup>F]BTF has the fundamental features of an OX1R PET probe, and further studies may lead to the development of more useful probes.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.jmedchem.4c01090","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
The orexin 1 receptor (OX1R) has been suggested to be involved in the reward and autonomic nervous systems. Positron emission tomography (PET) of OX1R contributes to elucidating its role and developing new drugs. However, there are no useful PET probes for in vivo imaging of OX1R. Here, we newly designed and synthesized 18F-labeled 1,4-diazepane derivatives and evaluated their utilities as OX1R PET probes. In particular, BTF showed high and selective binding affinity for OX1R. In a biodistribution study using normal mice, [18F]BTF exhibited brain uptake, and radioactivity in the brain was significantly decreased by preinjection of unlabeled BTF. In a PET/CT study, it was suggested that [18F]BTF has the potential to visualize high-expression regions of OX1R in the normal mouse brain. Collectively, [18F]BTF has the fundamental features of an OX1R PET probe, and further studies may lead to the development of more useful probes.
期刊介绍:
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.