Aromatic linker variations in novel dopamine D 2 and D 3 receptor ligands.

Autor: Di Biase C; Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Duesseldorf, Germany., Leitzbach L; Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Duesseldorf, Germany., Frank A; Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Duesseldorf, Germany., Zivkovic A; Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Duesseldorf, Germany., Stark H; Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Duesseldorf, Germany.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2024 Aug; Vol. 357 (8), pp. e2400071. Date of Electronic Publication: 2024 May 12.
DOI: 10.1002/ardp.202400071
Abstrakt: Dopamine D 2 -like receptors, especially D 2 and D 3 receptor subtypes, are important targets of antipsychotic agents. Many of these antipsychotics share an aliphatic linker element between a protonable amine group and an acyl-like moiety. Here, we have modified this aliphatic linker into phenylmethyl and phenylethyl linkers substituted in different positions. The design, synthesis, and in vitro evaluation of 18 dopamine D 2 and D 3 receptor ligands were performed in this study. Using a radioligand displacement assay, all ligands were found to have modest nanomolar affinity to D 2 R and D 3 R. N-(4-{2-[4-(2-Methoxyphenyl)piperazin-1-yl]ethyl}phenyl)acetamide (6c) demonstrates the highest D 3 R and D 2 R affinity values (pK i values of 7.83 [D 2 R] and 8.04 [D 3 R]), featuring a slight preference to D 3 R. This derivative can be taken as a reference structure for the development of a new class of D 2 R and D 3 R ligands.
(© 2024 The Authors. Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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