Syntheses of O-Methylasparvenone-derived Serotonin-receptor Antagonists

Article abstract of DOI:10.1002/hlca.19980810306

Based on O-methylasparvenone (1), a N-free 5HT_2C antagonist with moderate affinity (pK_i = 6.7), derivatives bearing dimethylamino (7), (dimethylamino)methyl (17, 18, 21, and 22), and aminomethyl substituents (26) in place of the benzylic OH group of 1 as well as pyrrolidine- (33) and piperidine-fused derivatives (29, 43, and 45) were synthesized.In contrast to the lead structure 1, these new ligands were active in vivo in the rat.The tricycles 33 and 45 display high affinities for the 5HT_2C receptor (pK_i = 8).