dc.contributor.author | Granda, Michael L. | |
dc.contributor.author | Carlin, Stephen M. | |
dc.contributor.author | Moseley, Christian K. | |
dc.contributor.author | Neelamegam, Ramesh | |
dc.contributor.author | Mandeville, Joseph B. | |
dc.contributor.author | Hooker, Jacob M | |
dc.date.accessioned | 2017-07-24T17:15:30Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | Granda, Michael L., Stephen M. Carlin, Christian K. Moseley, Ramesh Neelamegam, Joseph B. Mandeville, and Jacob M. Hooker. 2013. “Synthesis and Evaluation of Methylated Arylazepine Compounds for PET Imaging of 5-HT2cReceptors.” ACS Chemical Neuroscience 4 (2) (February 20): 261–265. doi:10.1021/cn300223d. | en_US |
dc.identifier.issn | 1948-7193 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:33490453 | |
dc.description.abstract | The serotonin 5-HT2c receptor is implicated in a number of diseases including obesity, depression, anxiety, and schizophrenia. In order to ascribe the role of 5-HT2c in these diseases, a method for measuring 5-HT2c density and function in vivo, such as with positron emission tomography (PET), must be developed. Many high-affinity and relatively selective ligands exist for 5-HT2c but cannot be accessed with current radiosynthetic methods for use as PET radiotracers. We propose that N-methylation of an arylazepine moiety, a frequent structural feature in 5-HT2c ligands, may be a suitable method for producing new radiotracers for 5-HT2c. The impact of N-methylation has not been previously reported. For the agonists that we selected herein, N-methylation was found to increase affinity up to 8-fold without impairing selectivity. Compound 5, an N-methylated azetidine-derived arylazepine, was found to be brain penetrant and reached a brain/blood ratio of 2.05:1. However, our initial test compound was rapidly metabolized within 20 min of administration and exhibited high nonspecific binding. N-Methylation, with 16 ± 3% isolated radiochemical yield (decay corrected), is robust and may facilitate screening other 5-HT2c ligands as radiotracers for PET. | en_US |
dc.description.sponsorship | Chemistry and Chemical Biology | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | American Chemical Society (ACS) | en_US |
dc.relation.isversionof | doi:10.1021/cn300223d | en_US |
dash.license | META_ONLY | |
dc.subject | serotonin | en_US |
dc.subject | PET imaging | en_US |
dc.subject | carbon-11 | en_US |
dc.subject | 5-HT2c agonist | en_US |
dc.title | Synthesis and Evaluation of Methylated Arylazepine Compounds for PET Imaging of 5-HT 2c Receptors | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | ACS Chemical Neuroscience | en_US |
dash.depositing.author | Hooker, Jacob M | |
dash.embargo.until | 10000-01-01 | |
dc.identifier.doi | 10.1021/cn300223d | * |
dash.contributor.affiliated | Mandeville, Joseph | |
dash.contributor.affiliated | Hooker, Jacob | |
dash.contributor.affiliated | Neelamegam, Ramesh | |