189061-44-7Relevant articles and documents
Multitarget Compounds for Bipolar Disorder: From Rational Design to Preliminary Pharmacokinetic Evaluation
Di Martino, Rita Maria Concetta,Bottegoni, Giovanni,Seghetti, Francesca,Russo, Debora,Penna, Ilaria,De Simone, Alessio,Ottonello, Giuliana,Mandrup Bertozzi, Sine,Armirotti, Andrea,Bandiera, Tiziano,Belluti, Federica,Cavalli, Andrea
, p. 949 - 954 (2020)
Due to the complex and multifactorial nature of bipolar disorder (BD), single-target drugs have traditionally provided limited relief with no disease-modifying effects. In line with the polypharmacology paradigm, we attempted to overcome these limitations by devising two series of multitarget-directed ligands endowed with both a partial agonist profile at dopamine receptor D3 (D3R) and inhibitory activity against glycogen synthase kinase 3 beta (GSK-3β). These are two structurally unrelated targets that play independent, yet connected, roles in cognition and mood regulation. Two compounds (7 and 10) emerged as promising D3R/GSK-3β multitarget-directed ligands with nanomolar activity at D3R and low-micromolar inhibition of GSK-3β, thereby confirming, albeit preliminarily, the feasibility of our strategy. Furthermore, 7 showed promising drug-like properties in stability and pharmacokinetic studies.
NGB 2904 NGB 2849: Two highly selective dopamine D3 receptor antagonists
Yuan, Jun,Chen, Xi,Brodbeck, Robbin,Primus, Renee,Braun, Julia,Wasley, Jan W. F.,Thurkauf, Andrew
, p. 2715 - 2718 (1998)
N-(4-[4-{2, 3-dichlorophenyl}-1-piperazinyl]butyl(-3- fluorenylcarboxamide and N-(4-(4-{2,3-dichlorophenyl}-1-piperazinyl]butyl)- 2-biphenylenylcarboxamide were prepared in several steps from 2,3- dichloroaniline. These compounds were identified as highly selective dopamine D3 receptor antagonists.
Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands
Elek, Milica,Djokovic, Nemanja,Frank, Annika,Oljacic, Slavica,Zivkovic, Aleksandra,Nikolic, Katarina,Stark, Holger
, (2021/02/26)
Dopamine is an important neurotransmitter in the human brain and its altered concentrations can lead to various neurological diseases. We studied the binding of novel compounds at the dopamine D2 (D2R) and D3 (D3/sub
Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands
Chen, Peng-Jen,Taylor, Michelle,Griffin, Suzy A.,Amani, Armaghan,Hayatshahi, Hamed,Korzekwa, Kenneth,Ye, Min,Mach, Robert H.,Liu, Jin,Luedtke, Robert R.,Gordon, John C.,Blass, Benjamin E.
supporting information, p. 2690 - 2694 (2019/08/07)
As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.
