Hiller C, Kling R, Heinemann FW, Meyer K, Hübner H, Gmeiner P (2013)
Publication Language: English
Publication Type: Journal article, Original article
Publication year: 2013
Original Authors: Hiller C., Kling R.C., Heinemann F.W., Meyer K., Hübner H., Gmeiner P.
Publisher: American Chemical Society
Book Volume: 56
Pages Range: 5130-5141
Journal Issue: 12
DOI: 10.1021/jm400520c
Dopaminergics of types 1 and 2 incorporating a conjugated enyne as an atypical catechol-simulating moiety were synthesized in enantiomerically pure form and investigated for their metabolic stability. Radioligand binding studies indicated high affinity to D-like receptors. The test compounds were evaluated for their ability to differentially activate distinct signaling pathways. Measurement of D- and D-mediated [ S]GTPγS incorporation in the presence of coexpressed Gα and Gα subunits showed significantly biased receptor activation for several test compounds. Thus, the 2-azaindolylcarboxamide (S)-2a exhibited substantial functional selectivity for D-promoted G activation over G coupling. The most significant bias was determined for the triazolylalkoxy-substituted benzamide (S)-2c that displayed higher potency for G activation than for G coupling at the D subtype. Functional selectivity for β-arrestin recruitment over G activation was observed for the biphenylcarboxamide (R)-1 and the 2-benzothiophenylcarboxamide (S)-2d, whereas the 2-substituted azaindole (S)-2a preferred β-arrestin recruitment compared to G coupling. © 2013 American Chemical Society.
APA:
Hiller, C., Kling, R., Heinemann, F.W., Meyer, K., Hübner, H., & Gmeiner, P. (2013). Functionally selective dopamine D2/D3 receptor agonists comprising an enyne moiety. Journal of Medicinal Chemistry, 56(12), 5130-5141. https://doi.org/10.1021/jm400520c
MLA:
Hiller, Christine, et al. "Functionally selective dopamine D2/D3 receptor agonists comprising an enyne moiety." Journal of Medicinal Chemistry 56.12 (2013): 5130-5141.
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