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
A. Pigott, X.-p. Huang, J.d. Mccorvy, B.l. Roth, S. Frescas, D.e. Nichols
UNC Libraries August 7, 2020 DOI: 10.17615/g6m9-bg59 via OpenAlex
Summary
Replacing the ethylamine side chain of two psychedelic amphetamine derivatives, DOI and DOB, with a cyclopropylamine group produced new compounds that bind tightly to the 5-HT2 family of serotonin receptors. The most potent version had the (-)-(1R,2S)- configuration. However, these cyclopropane analogues also showed increased affinity for several other serotonin receptor subtypes beyond 5-HT2A and 5-HT2B. At appropriate doses, they may still be useful research tools for probing 5-HT2 receptor function, but their selectivity for 5-HT2A receptors is lower than that of the original compounds.
Study at a glance
| Characteristics | Peer reviewed |
|---|---|
| Keywords | Stereochemistry Cyclopropane reaction mechanisms |
| Key finding | 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.