Design, synthesis and dopamine D4 receptor binding activities of new N-heteroaromatic 5/6-ring Mannich bases

A series of phenylpiperazine-methyl-substituted 1H-pyrrolo[2,3-c] pyridine, imidazo[1,2-c]-, pyrrolo[2,3-d]- and pyrrolo[3,2-d] pyrimidines were prepared as selective dopamine D4-ligands. The pyrrolo[2,3-d] pyrimidine derivatives 12d (K-i = 1,9 nM) and 34d (K-i = 2,4 nM) as well as the pyrrolo[3,2-d] pyrimidine Mannich base 49f (K-i = 2,8 nM) showed high dopamine D4 receptor activity superior to the atypical antipsychotic agent clozapine. (C) 2009 Elsevier Ltd. All rights reserved.