Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents.

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Peprah K, Zhu XY, Eyunni SV, Setola V, Roth BL, Ablordeppey SY

Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents.

Bioorg Med Chem. 2012 Feb 1;20(3):1291-7. doi: 10.1016/j.bmc.2011.12.019. Epub 2011 Dec 22.

PubMed ID

22245230 [ View in PubMed

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Abstract

Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contributes to changes in binding to the receptors of interest. This strategy has resulted in the identification of several new agents, compounds 16, 18, 19, 23, 24 and 25, with binding profiles which satisfy our stated criteria for agents to act as potential atypical antipsychotics. This research demonstrates that haloperidol can serve as a useful lead in the identification and design of new agents that target multiple receptors associated with antipsychotic pharmacology.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Clozapine	Histamine H1 receptor	Ki (nM)	1.8	N/A	N/A	Details
Clozapine	Muscarinic acetylcholine receptor M1	Ki (nM)	1.8	N/A	N/A	Details
Haloperidol	Dopamine D3 receptor	Ki (nM)	4.6	N/A	N/A	Details