Conformational analysis of the dopamine-receptor agonist 5-hydroxy-2-(dipropylamino)tetralin and its C(2)-methyl-substituted derivative

摘要: The conformational preferences of the dopamine (DA) receptor agonist 5-hydroxy-2-(di-n-propylamino)tetralin (1) and DA-inactive 5-hydroxy-2-methyl-2-(di-n-propylamino)tetralin (2) have been studied by use molecular mechanics (MMP2) calculations NMR spectroscopy. A good agreement is demonstrated between experimentally determined (by NMR) calculated MMP2) distribution 1 2. In addition, there a bond distances angles in X-ray structure hydrobromide those corresponding MMP2 conformation. Results obtained demonstrate that energetically preferred conformations 2 are different: Compound preferentially adopts half-chair with pseudoequatorial nitrogen substituent whereas low-energy compound pseudoaxial substituent. However, results also indicate difference too small to account for dopaminergic inactivity Therefore it suggested steric bulk C(2)-methyl group per se prevents proper alignment (2S)-2 DA receptors.