• Journal Article

Evaluation of structural effects on 5-HT receptor antagonism by aporphines: Identification of a new aporphine with 5-HT antagonist activity

Citation

Ponnala, S., Gonzales, J., Kapadia, N., Navarro, H., & Harding, W. W. (2014). Evaluation of structural effects on 5-HT receptor antagonism by aporphines: Identification of a new aporphine with 5-HT antagonist activity. Bioorganic and Medicinal Chemistry Letters, 24(7), 1664-1667. DOI: 10.1016/j.bmcl.2014.02.066

Abstract

A set of aporphine analogs related to nantenine was evaluated for antagonist activity at 5-HT2A and alpha1A 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 alpha1A antagonism. A slight eutomeric preference for the R enantiomer of nantenine was observed in relation to alpha1A antagonism