Synthesis of Dihydrofuroaporphine Derivatives: Identification of a Potent and Selective Serotonin 5-HT1A Receptor Agonist
Year: 2009
Type: article
Abstract: A series of new aporphine analogues were synthesized and pharmacologically evaluated. 11-Allyloxy-(17), 11-propargyloxy-(20), and dihydrofuro-(19) aporphines displayed the highest affinity at the 5-HT(1A) receptor with K(i) values of 12.0, 14.0, and 6.7 nM, respectively. The high binding potential of the diastereomeric mixture of aporphine 19 was found residing in the cis-diastereomer (cis-19). [(35)S]GTP gamma S function assays on 5-HT(1A) receptor indicated that aporphines 17 and 20 were partial agonists, while trans-19 behaved as a high efficacy full antagonist and cis-19 was a full agonist. The agonistic property of cis-19 at the 5-HT(1A) receptor was further confirmed in vitro and in vivo. This compound may be useful as a potential treatment for anxiety.
Source: Journal of Medicinal Chemistry
DOI: 10.1021/jm9015763
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2039798317