2-Phenyl-4(5)-[[4-(pyrimidin-2- yl)piperazin-1-yl]methyl]imidazole. A Highly Selective Antagonist at Cloned Human D₄ Receptors

Searching for multi-target antipsychotics: Discovery of orally active heterocyclic N-phenylpiperazine ligands of D2-like and 5-HT1A receptors

“…Derivatives presenting a biphenyl, 1-phenylpyrrole, 2-phenylpyrrole, 2-phenylimidazole, 4-phenylthiazole, and 3-phenylpiridine systems were successfully described as D 4 -selective ligands with different intrinsic activity. 22,31,[35][36][37][38][39][40][41][42][43][44] An important member of this series of compounds is the 2-phenylimidazole derivative NGD-94-1 (30) (Fig. 2), considered as a selective D 4 full antagonist (K i = 3.6 nM) by some authors 44 although others reported that it was able to activate human recombinant dopamine D 4.4 receptors expressed in HEK293 cells.…”

“…22 Some of the studies cited above carried on with biarylmethylamine derivatives also describe compounds with considerable affinity for the 5-HT 1A receptors. 22,35,39,42,44 Both NGD-94-1 (30) and FAUC 2020 (31) bind with high affinity to this subtype of serotonin receptor (K i = 180 and 37 nM, respectively). 22,44 Indeed, there is a high molecular similarity between the compounds assayed in present work, NGD-94-1 (30), FAUC 2020 (31), and bifeprunox (3), a mixed D 2 partial agonist (K i = 2.2 nM) and 5-HT 1A agonist Scheme 1.…”

Preparation of derivatives of 1‐(2‐pyrimidinyl)piperazine as potential antianxiety, antidepressant, and antipsychotic agents

“…The compound called NGD94-1, prepared by Thurkauf and coworkers [19], has exhibited antipsychotic activity in a model system in rats. This activity has prompted evaluation of this compound as a possible treatment for schizophrenia [19][20][21].…”

“…This activity has prompted evaluation of this compound as a possible treatment for schizophrenia [19][20][21]. NGD94-1 is a derivative of 1-(2-pyrimidinyl)piperazine.…”

Esquizofrenia: quarenta anos da hipótese dopaminérgica sob a ótica da Química Medicinal

“…O emprego de estratégias racionais de modificação molecular sobre a estrutura da clozapina (5), incluindo trocas isotéricas, simplificações estruturais, contrações de anel, não lograram na obtenção de análogos com perfis de bioatividade e toxicidade significativamente superiores ao protótipo [63][64][65] , mas permitiram hierarquizar as sub-unidades moleculares de maior relevância para a atividade central, tornando possível a obtenção de novos derivados heterocíclicos, e.g. 31 66 , apresentando seletividade funcional (…”