Journal of Medicinal Chemistry
September 1, 2002
David E. Nichols, Stewart Frescas, Danuta Marona‐lewicka et al.
89 citations
Lysergic acid amides containing a rigid dimethylazetidine ring—a constrained version of diethylamine—were synthesized and tested for hallucinogenic activity. The (S,S)-(+)-2,4-dimethylazetidine lysergamide showed slightly greater LSD-like behavioral effects in rats than LSD itself and had the highest affinity and functional potency at the serotonin 5-HT(2A) receptor, the presumed target for hallucinogens. Its receptor profile across a panel of screens most closely matched that of LSD. In contrast, the cis- and (R,R)-trans-dimethylazetidine lysergamides were less potent. These results suggest that the N,N-diethyl groups of LSD bind optimally in a conformation different from that seen in the solid state. Incorporating isomeric dialkylazetidines into other molecules may help model active conformations of dialkylamines and dialkylamides.
Beilstein Journal of Organic Chemistry
October 8, 2012
Adam Pigott, Stewart Frescas, John D. Mccorvy et al.
19 citations
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.
UNC Libraries
October 31, 2020
Adam Pigott, Bryan L. Roth, Xi‐ping Huang et al.
Replacing the ethylamine side chain of the psychedelic compounds DOI and DOB with a cyclopropylamine group produced new molecules that bind strongly to 5-HT2 family serotonin receptors. The most potent version had the (−)-(1R,2S)-configuration. However, these cyclopropane analogs also showed increased affinity for other serotonin receptor subtypes beyond 5-HT2A and 5-HT2B, making them less selective than the original compounds. At appropriate doses, they may serve as research tools for studying 5-HT2 receptor function, but their reduced selectivity for 5-HT2A receptors must be considered.