Trans-2-(2,5-dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT 2 receptor family
Adam Pigott, X.-p. Huang, John D. Mccorvy, B.l. Roth, S. Frescas, D.e. Nichols
UNC Libraries August 7, 2020 DOI: 10.17615/g6m9-bg59 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Peer reviewed |
|---|---|
| Keywords | Stereochemistry Cyclopropane reaction mechanisms |
| Key points | Cyclopropylamine analogues of DOI and DOB have high affinity for 5-HT2 receptors but lower selectivity for 5-HT2A than the parent compounds. |
Abstract
A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4- iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT 2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (-)-(1R,2S)- configuration. Screening for affinity at various serotonin receptor subtypes, however, revealed that the cyclopropane congeners also had increased affinity at several sites in addition to the 5-HT 2A and 5-HT 2B receptors. Therefore, at appropriate doses - although (-)-4 and (-)-5 may be useful as tools to probe 5-HT 2 receptor function - one would need to be mindful that their selectivity for 5-HT 2A receptors is somewhat less than for DOI itself.