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 34 d (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.
Linz
Sabine
S
Department Chemie und Pharmazie, Lehrstuhl Pharmazeutische Chemie, Friedrich-Alexander-Universität, Erlangen, Germany.
Müller
Jörg
J
Hübner
Harald
H
Gmeiner
Peter
P
Troschütz
Reinhard
R
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016466:CHO Cells; D002417:Cattle; D003024:Clozapine / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D010879:Piperazines; D011743:Pyrimidines; D011954:Receptors, Dopamine; D050638:Receptors, Dopamine D4; D003024:Clozapine; C031503:phenylpiperazine