Conformational energy differences between side chain alkylated analogues of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane.
H J Weintraub, D E Nichols, A Makriyannis, S W Fesik
Journal of Medicinal Chemistry March 1980 DOI: 10.1021/jm00177a030 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical conformational analysis with experimental NMR validation Peer reviewed |
|---|---|
| Measures | 13C spin-lattice relaxation times (T1) |
| Key findings | Conformational energies in a previously proposed active region allowed the compounds to be ranked by potency, and 13C spin-lattice relaxation time (T1) measurements confirmed that the dimethyl analogue has very restricted conformational freedom while the cyclopropane analogue is more flexible, matching the theoretical predictions. |
Abstract
Theoretical conformational energy calculations were carried out for the (+) and (-) isomers of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM, STP). Energies were also calculated for two analogues of DOM, 1-amino-1-(2,5-dimethoxy-4-methylbenzyl)cyclopropane and 1-(2,5-dimethoxy-4-methylphenyl)-2-methyl-2-aminopropane. This method utilized classical, empirical potential-energy functions. A previously proposed active conformational region was studied. Compounds could be ranked in order of potency based on relative conformational energies in this region. Measurement of 13C spin--lattice relaxation times (T1) for the two alpha, alpha-disubstituted DOM analogues confirmed theoretical predictions of very restricted conformational freedom for the dimethyl compound but more flexibility for the cyclopropane analogue.