title: Semisynthetic Studies on and Biological Evaluation of N-Methyllaurotetanine Analogues as Ligands for 5-HT Receptors.
abstract: N-Methyllaurotetanine (1) has been reported to display good affinity for the 5-HT1A receptor, but no structure-affinity studies have been performed to date. The commercially available alkaloid boldine (2) was used as the starting material for synthesis of various C-9 alkoxy analogues of N-methyllaurotetanine in order to gauge the effect of C-9 alkylation on affinity and selectivity at 5-HT1A, 5-HT2A, and 5-HT7 receptors. Mitsunobu reactions were implemented in the alkylation steps leading to the analogues. Modest improvement in 5-HT1A affinity was observed upon alkylation for most analogues. Thus, the C-9 hydroxy group of 1 is not critical for affinity to the 5-HT1A receptor. Some analogues displayed high affinity for the 5-HT7 receptor, comparable to N-methyllaurotetanine, with moderate selectivity vs 5-HT1A and 5-HT2A receptors.
authors.affiliation: Department of Chemistry, Hunter College, City University of New York, , 695 Park Avenue, New York, New York 10065, United States.
authors.forename: Sudharshan
authors.initials: S
authors.lastname: Madapa
authors.affiliation: Department of Chemistry, Hunter College, City University of New York, , 695 Park Avenue, New York, New York 10065, United States.
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Harding
mesh_terms: D001060:Aporphines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001060:Aporphines; D008024:Ligands; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; C000600631:N-methyllaurotetanine; C011686:boldine