2-amino-2-oxazolines, VII: 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-4-piperazino)methyl-2-amino-2-oxazolines has been prepared and screened for antidepressant activity. Their lipophilic behaviour has been discussed in relation to the nature and the position of substituents on the aromatic ring. The influence of steric effects on the pharmacological activity has been investigated using experimental methods (X-ray diffraction, NMR) and theoretical calculations (semi-empirical quantum mechanics). The ortho-substitution on the phenyl ring or the C-alpha substitution on the piperazine ring by a methyl group 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 the antidepressant activity. Using NMR, only the influence of the ortho-substitution has been observed.
Bosc
J J
JJ
Laboratoire de chimie physique, Université de Bordeaux II, France.
Forfar
I
I
Jarry
C
C
Laguerre
M
M
Carpy
A
A
D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001831:Body Temperature / Q000187:drug effects; D051379:Mice; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D012110:Reserpine / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000928:Antidepressive Agents; D010080:Oxazoles; D010879:Piperazines; D012110:Reserpine