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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 ?1A 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 ?1A antagonism. A slight eutomeric preference for the R enantiomer of nantenine was observed in relation to ?1A antagonism.

SUBMITTER: Ponnala S

PROVIDER: S-EPMC4022183 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Ponnala Shashikanth S Gonzales Junior J Kapadia Nirav N Navarro Hernan A HA Harding Wayne W WW

Bioorganic & medicinal chemistry letters 20140304 7

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 identif ...[more]

PMID: 24630561

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