CONFORMATIONAL-ANALYSIS OF 2,3,6,7-TETRAHYDROAZEPINES WITH IMPLICATIONS FOR D1-SELECTIVE BENZAZEPINES

A conformational study of the 2,3,6,7-tetrahydroazepine (THA) and closely related systems has been carried out using MM3 and CHARMm molecular mechanics, AMI semiempirical, as well as Hartree-Fock and local density functional (LDF) ab initio methods. For THA, all methods give similar optimal geometries; however, only MM3 agrees with the Hartree-Fock calculations using a 6-31G* basis set and LDF in the rank order of energies and nature of the stationary points characterized. AM1 shows serious disagreements with those results. Tetrahydrobenzazepines and a D1 receptor agonist containing the THA nucleus were studied using CHARMm, MM3, and AM1 calculations. All methods provide similar descriptions of the geometries of the conformations accessible to these compounds. However, the same disparities in the rank order of energies are observed.