VUF-8929

A new series of diphenylalkylamine congeners of prenylamine have been assayed in binding experiments on rat striatal membrane preparationsThe aim was to ascertain the influence of structural modifications and lipophilicity on their interaction with the [³H]tyramine-labeled vesicular transporter for dopamine.Thirteen compounds potently inhibited the specific binding of [³H]tyramine, with nanomolar K_i values in the range of those of established markers for the vesicular transporter of dopamine.Less lipophilic compounds displayed higher affinity for the energy-dependent amine transporter.

Quant. structure-activity relationships for a series of 71 diphenylalkylamines which possesses a relatively high capacity of interfering with calmodulin have been reported.Partial least square (PLS) anal. was used to obtain detailed information on structural features affecting calmodulin antagonistic activity.Apart from lipophilicity, structural parameters also strongly influence the activity.Chain length, the presence and/or absence of the Me group vicinal to the nitrogen atom, the methylation of the nitrogen atom as well as the presence of the oxygen as heteroatom in combination with benzhydryl substitution have been indicated as the most important mol. descriptors.The model thus provided by PLS anal. successfully predicted the biol. activities of addnl. newly synthesized prenylamine derivatives