【文章名】Advances toward New Antidepressants with Dual Serotonin Transporter and 5-HT1A Receptor Affinity within a Class of 3-Aminochroman Derivatives. Part 2.
[摘要]：(Heterocyclic Compounds (One Hetero Atom)) Section Novel compds. combining a 5-HT1A moiety (3-aminochroman scaffold) and a 5-HT transporter (indole analogs) linked through a common basic nitrogen via an alkyl chain attached at the 1- or 3-position of the indole were evaluated for dual affinity at both the 5-HT reuptake site and the 5-HT1A receptor. Compds. of most interest were found to have a 5-carbamoyl-8-fluoro-3-amino-3,4-dihydro-2H-1-benzopyran linked to a 3-alkylindole (straight chain), more specifically substituted with a 5-fluoro, 5-cyano, or 5,7-difluoro. Several factors contributed to 5-HT1A affinity, serotonin rat transporter affinity, and functional antagonism in vitro. Although most of our analogs showed good to excellent affinities at both targets, specific features such as cyclobutyl substitution on the basic nitrogen and stereochem. at the 3-position of the chroman moiety seemed necessary for antagonism at the 5-HT1A receptor. Branched linkers seemed to impart antagonism even as racemates; however, the potency of these analogs in the functional assay was not desirable enough to further pursue these compds.
