Bioorganic & Medicinal Chemistry 2009-02-15

Synthesis and evaluation of ligands for D2-like receptors: the role of common pharmacophoric groups.

Donald M N Sikazwe, Nancy T Nkansah, Ramazan Altundas, Xue Y Zhu, Bryan L Roth, Vincent Setola, Seth Y Ablordeppey

Index: Bioorg. Med. Chem. 17(4) , 1716-23, (2009)

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Abstract

Arylcycloalkylamines, such as phenyl piperidines and piperazines and their arylalkyl substituents, constitute pharmacophoric groups exemplified in several antipsychotic agents. A review of previous reports indicates that arylalkyl substituents can improve the potency and selectivity of the binding affinity at D(2)-like receptors. In this paper, we explored the contributions of two key pharmacophoric groups, that is, 4'-fluorobutyrophenones and 3-methyl-7-azaindoles, to the potency and selectivity of synthesized agents at D(2)-like receptors. Preliminary observation of binding affinities indicates that there is little predictability of specific effects of the arylalkyl moieties but the composite structure is responsible for selectivity and potency at these receptors.