NEW SPIROHYDANTOIN DERIVATIVES - SYNTHESIS, PHARMACOLOGICAL EVALUATION, AND MOLECULAR MODELING STUDY

A series of new arylpiperazinylpropyl derivatives of 8/6-phenyl-1,3-diazaspiro[4.5]decan-2,4-dione and spiro[imidazolidine-4,1'-indene/naphthalene]-2,5-dione was synthesized and their affinity was evaluated toward serotonin 5-HTIA, 5-HT2A, 5-HT7 receptors, dopaminergic D2, D3 receptors, adrenergic ox, receptors, and serotonin transporter (SERT). The highest affinity for serotonin 5-HT1A/2A/7 receptors was found for compounds containing a tetralin or indane moiety in the imide part. Among these, two compounds (19, 20) were selected for further pharmacological in vivo studies. A binding mode of representative molecule 19, which behaved as a 5-HT1A agonist and weak 5-HT7 antagonist in the site of 5-HT 1A/7, was also analyzed in computational stud- ies. Moreover, two highly selective (9 and HI) 5-HT₂A receptor antagonists were obtained.