Conformation by NMR of two tetralin-based receptor ligands

The conformation in solution of 1-phenyl-3-propionamido-1,2,3,4-tetrahydronaphthalene and 1-phenyl-3-(N,N-dimethylamino)-1,2,3,4-tetrahydronaphthalene has been determined by a combination of nuclear magnetic resonance measurements and molecular mechanics calculations. The results indicate that in the cis isomers the cyclohexene ring is in a locked conformation and the trans isomers correspond to a mixture of the two inverted half chairs. Moreover, the data allowed the identification of the two purposely-synthesized geometrical isomers of 1-phenyl-3-propionamidotetralin. Binding studies on melatonin receptor subtypes showed that the (+/-)-cis-1-phenyl-3-propionamido-1,2,3,4-tetrahydronaphthalene has higher affinity and selectivity ratio toward the MT(2) subtype than the (+/-)-trans-isomer.