Pirzer A, Lasch R, Friedrich H, Hübner H, Gmeiner P, Heinrich M (2019)
Publication Type: Journal article, Original article
Publication year: 2019
Book Volume: 62
Pages Range: 9658-9679
DOI: 10.1021/acs.jmedchem.9b01085
Many subtype-selective dopamine receptor ligands developed for the D2-D4 family incorporate a 1-arylpiperazine-derived primary recognition motif, which is connected to a lipophilic moiety occupying an extended binding pocket (EBP) of the receptor via an aliphatic linker of variable lengths. The evaluation of a novel group of dopamine receptor ligands now showed that highly subtype-selective ligands [up to Ki(D4.4) = 0.25 nM, D2L/D4.4 = 320, D3/D4.4 = 710 for APH199 (17)] can be obtained by choosing a relatively large and conformationally flexible 1-benzyl-1-phenylsemicarbazide substructure to fill the EBP. The novel chemotype APH199 (17) was found to act as a full agonist at the D4 receptor showing significant bias toward G protein activation over β-arrestin recruitment in comparison to quinpirole.
APA:
Pirzer, A., Lasch, R., Friedrich, H., Hübner, H., Gmeiner, P., & Heinrich, M. (2019). Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D4 Receptor Agonists with High Subtype Selectivity. Journal of Medicinal Chemistry, 62, 9658-9679. https://doi.org/10.1021/acs.jmedchem.9b01085
MLA:
Pirzer, Anna, et al. "Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D4 Receptor Agonists with High Subtype Selectivity." Journal of Medicinal Chemistry 62 (2019): 9658-9679.
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