Evaluation of structural effects on 5-HT_2A receptor antagonism by aporphines: Identification of a new aporphine with 5-HT_2A antagonist activity

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• 作者：Shashikanth Ponnala^a ; Junior Gonzales^a ; ^b ; Nirav Kapadia^a ; ^b ; Hernan A. Navarro^c ; Wayne W. Harding^a ; ^b ; ^{whardi@hunter.cuny.edu" class="auth_mail}
• 关键词：Aporphine ; Nantenine ; 5-HT2A ; 伪1A ; Antagonist ; Structure&ndash ; activity relationship (SAR)
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：1 April, 2014
• 年：2014
• 卷：24
• 期：7
• 页码：1664-1667
• 全文大小：468 K

文摘

A set of aporphine analogs related to nantenine was evaluated for antagonist activity at 5-HT_2A and 伪_1A adrenergic receptors.

With regards to 5-HT_2A receptor antagonism, a C2 allyl group is detrimental to activity. The chiral center of nantenine is not important for 5-HT_2A antagonist activity, however the N6 nitrogen atom is a critical feature for 5-HT_2A antagonism.

Compound 12b was the most potent 5-HT_2A 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 伪_1A antagonism. A slight eutomeric preference for the R enantiomer of nantenine was observed in relation to 伪_1A antagonism.