title: Evaluation of structural effects on 5-HT(2A) receptor antagonism by aporphines: identification of a new aporphine with 5-HT(2A) antagonist activity.
abstract: A set of aporphine analogs related to nantenine was evaluated for antagonist activity at 5-HT2A and α1A adrenergic receptors. With regards to 5-HT2A receptor antagonism, a C2 allyl group is detrimental to activity. The chiral center of nantenine is not important for 5-HT2A antagonist activity, however the N6 nitrogen atom is a critical feature for 5-HT2A antagonism. Compound 12b was the most potent 5-HT2A aporphine antagonist identified in this study and has similar potency to previously identified aporphine antagonists 2 and 3. The ring A and N6 modifications examined were detrimental to α1A antagonism. A slight eutomeric preference for the R enantiomer of nantenine was observed in relation to α1A antagonism.
authors.affiliation: Chemistry Dept., Hunter College, CUNY, 695 Park Avenue, NY 10065, USA.
authors.forename: Shashikanth
authors.initials: S
authors.lastname: Ponnala
authors.affiliation: Chemistry Dept., Hunter College, CUNY, 695 Park Avenue, NY 10065, USA; The Graduate Center, City University of New York, 365 5th Ave., NY 10016, USA.
authors.forename: Junior
authors.initials: J
authors.lastname: Gonzales
authors.affiliation: Chemistry Dept., Hunter College, CUNY, 695 Park Avenue, NY 10065, USA; The Graduate Center, City University of New York, 365 5th Ave., NY 10016, USA.
authors.forename: Nirav
authors.initials: N
authors.lastname: Kapadia
authors.affiliation: Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709, USA.
authors.forename: Hernan A
authors.initials: HA
authors.lastname: Navarro
authors.affiliation: Chemistry Dept., Hunter College, CUNY, 695 Park Avenue, NY 10065, USA; The Graduate Center, City University of New York, 365 5th Ave., NY 10016, USA. Electronic address: whardi@hunter.cuny.edu.
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Harding
mesh_terms: D001060:Aporphines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001060:Aporphines; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists
keywords: 5-HT(2A); Antagonist; Aporphine; Nantenine; Structure–activity relationship (SAR); α(1A)