trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family
Adam Pigott, Stewart Frescas, John D. Mccorvy, Xi‐ping Huang, Bryan L. Roth, David E. Nichols
Beilstein Journal of Organic Chemistry October 8, 2012 DOI: 10.3762/bjoc.8.194 via OpenAlex
Summary
Replacing the ethylamine side chain of two psychedelic amphetamine derivatives, DOI and DOB, with a cyclopropylamine moiety produced compounds with high affinity for the 5-HT(2) family of serotonin receptors. The more potent stereoisomer of these cyclopropane analogues had the expected (-)-(1R,2S)-configuration. However, the cyclopropane congeners also showed increased affinity at several other serotonin receptor subtypes beyond 5-HT(2A) and 5-HT(2B). While at appropriate doses the compounds may serve as tools to probe 5-HT(2) receptor function, their selectivity for 5-HT(2A) receptors is somewhat less than that of DOI itself.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Ethylamine Moiety Stereochemistry 5-HT Receptor G protein-coupled receptor |
| Citations | 19 |
| Key finding | Cyclopropylamine analogues of DOI and DOB retain high affinity for 5-HT(2) receptors but show reduced selectivity for 5-HT(2A) compared to 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.