2-AMINO-2-OXAZOLINES .7. INFLUENCE OF STRUCTURAL PARAMETERS ON THE ANTIDEPRESSANT ACTIVITY OF 5-(1-ARYL-4-PIPERAZINO)METHYL-2-AMINO-2-OXAZOLINES

A series of 5-(1-aryl-3-piperazino)methyl-2-amino-2-oxazolines has bee n prepared and screened for antidepressant activity. Their lipophilic behaviour has been discussed in relation to the nature and the positio n of substituents on the aromatic ring. The influence of steric effect s on the pharmacological activity has been investigated using experime ntal methods (X-ray diffraction, NMR) and theoretical calculations (se mi-empirical quantum mechanics). The ortho-substitution on the phenyl ring or the C-alpha substitution on the piperazine ring by a methyl gr oup results in the same effects i.e. an increase of the angle between the two rings up to 64 degrees (X-ray and calculation) and a loss of t he antidepressant activity. Using NMR, only the influence of the ortho -substitution has been observed.