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Bioorg Med Chem Lett. 2014 Apr 1;24(7):1664-7. doi: 10.1016/j.bmcl.2014.02.066. Epub 2014 Mar 4.

Evaluation of structural effects on 5-HT(2A) receptor antagonism by aporphines: identification of a new aporphine with 5-HT(2A) antagonist activity.

Author information

1
Chemistry Dept., Hunter College, CUNY, 695 Park Avenue, NY 10065, USA.
2
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.
3
Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709, USA.
4
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.

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.

KEYWORDS:

5-HT(2A); Antagonist; Aporphine; Nantenine; Structure–activity relationship (SAR); α(1A)

PMID:
24630561
PMCID:
PMC4022183
DOI:
10.1016/j.bmcl.2014.02.066
[Indexed for MEDLINE]
Free PMC Article

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