The 5-HT1A serotonin subtype functions as the presynaptic somatodendritic autoreceptor in the dorsal raphe nucleus and also as a postsynaptic receptor in the terminal field areas. Agonists of 5-HT1A reduce anxiety without the soporific side-effects observed in propanediol carbamate and benzodiazepine anxiolytics and studies in rats and primates indicate potential utility in relieving depression, stimulating appetite, and lowering elevated blood pressure. Of the many 5-HT1A agonists and antagonists reported in the literature, several have shown promise as potential neuroimaging agents, however, none have proven completely successful. One of the agonists which has, to date, not been investigated for its potential as a PET ligand, is Binospirone (MDL 73005). Due to its unique chemical structure, MDL 73005 offers a site for chemical elaboration, providing not only a position for radiolabelling, but also for structural modification which may enhance selectivity. Chemically, MDL 73005 is 8-[2-[[(2,3-Dihydro-1,4-benzodioxin-2- yl)methyl]amino]ethyl]-8-azaspiro[4.5]decane-7,9-dione, a secondary amine. This """"""""open"""""""" site is the position to be augmented. The work during 1995 has been a convergent synthesis of the parent compound. Two """"""""daughter"""""""" fragments were synthesized, each in several steps, and the final coupling of the fragments is presently underway.
