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• W2051277244 startingPage "2348" @default.
• W2051277244 abstract "A series of subtype selective dopamine D4 receptor ligands from the hetroarylmethylphenylpiperazine class have been discovered that exhibit a remarkable structure−activity relationship (SAR), revealing a substituent effect in which regiosubstitution on the terminal arylpiperazine ring can modulate functional or intrinsic activity. Other structure-dependent efficacy studies in the dopamine D4 field have suggested a critical interaction of the heteroarylmethyl moiety with specific protein microdomains in controlling intrinsic activity. Our studies indicate that for some binding orientations, the phenylpiperazine moiety also plays a key role in determining efficacy. These data also implicate a kinetic or efficiency term, contained within measured functional affinities for agonists, which support a sequential binding and conformational stabilization model for receptor activation. The structural similarity between partial agonist and antagonist, within this subset of ligands, and lack of bioisosterism for this substituent effect are key phenomena for these hypotheses." @default.
• W2051277244 created "2016-06-24" @default.
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• W2051277244 date "2004-03-23" @default.
• W2051277244 modified "2023-10-02" @default.
• W2051277244 title "Dopamine D₄ Ligands and Models of Receptor Activation: 2-(4-Pyridin-2-ylpiperazin-1-ylmethyl)-1<i>H</i>-benzimidazole and Related Heteroarylmethylarylpiperazines Exhibit a Substituent Effect Responsible for Additional Efficacy Tuning" @default.
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• W2051277244 doi "https://doi.org/10.1021/jm0305669" @default.
• W2051277244 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15084133" @default.
• W2051277244 hasPublicationYear "2004" @default.
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