| Autor: |
Naumiec GR; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health , Building 10, Room B3 C346A, 10 Center Drive, Bethesda, Maryland 20892-1003, United States., Jenko KJ; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health , Building 10, Room B3 C346A, 10 Center Drive, Bethesda, Maryland 20892-1003, United States., Zoghbi SS; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health , Building 10, Room B3 C346A, 10 Center Drive, Bethesda, Maryland 20892-1003, United States., Innis RB; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health , Building 10, Room B3 C346A, 10 Center Drive, Bethesda, Maryland 20892-1003, United States., Cai L; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health , Building 10, Room B3 C346A, 10 Center Drive, Bethesda, Maryland 20892-1003, United States., Pike VW; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health , Building 10, Room B3 C346A, 10 Center Drive, Bethesda, Maryland 20892-1003, United States. |
| Abstrakt: |
N-Methyl-d-aspartate (NMDA) receptor dysfunction has been linked to several neuropsychiatric disorders, including Alzheimer's disease, epilepsy, drug addiction, and schizophrenia. A radioligand that could be used with PET to image and quantify human brain NMDA receptors in the activated "open channel" state would be useful for research on such disorders and for the development of novel therapies. To date, no radioligands have shown well-validated efficacy for imaging NMDA receptors in human subjects. In order to discover improved radioligands for PET imaging, we explored structure-affinity relationships in N'-3-(trifluoromethyl)phenyl derivatives of N-aryl-N'-methylguanidines, seeking high affinity and moderate lipophilicity, plus necessary amenability for labeling with a positron-emitter, either carbon-11 or fluorine-18. Among a diverse set of 80 prepared N'-3-(trifluoromethyl)phenyl derivatives, four of these compounds (13, 19, 20, and 36) displayed desirable low nanomolar affinity for inhibition of [(3)H](+)-MK801 at the PCP binding site and are of interest for candidate PET radioligand development. |
