Conformational energy differences between side chain alkylated analogues of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane.

Weintraub HJ, Nichols DE, Makriyannis A, Fesik SW
J Med Chem. 1980 23 (3): 339-41

PMID: 7365752 · DOI:10.1021/jm00177a030

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.

MeSH Terms (6)

2,5-Dimethoxy-4-Methylamphetamine Amphetamines Molecular Conformation Solubility Stereoisomerism Thermodynamics

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