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.
Design, synthesis and evaluation of bitopic arylpiperazinephenyl-1,2,4-oxadiazoles as preferential dopamine D3 receptor ligands
Cao, Yongkai,Min, Chengchun,Acharya, Srijan,Kim, Kyeong-Man,Cheon, Seung Hoon
, p. 191 - 200 (2016)
The dopamine D3 receptor (D3R) was proposed as a therapeutic target for drug development to treat drug abuse and addiction and neuropsychiatric disorders. Several D3R-selective modulators over the dopamine D2 receptor (D2R) can avoid extrapyramidal sympto
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.
Design and synthesis of new potent 5-HT7 receptor ligands as a candidate for the treatment of central nervous system diseases
Drabczyk, Anna K.,Latacz, Gniewomir,Ja?kowska, Jolanta,Ku?aga, Damian,Pla?uk, Damian,Rózga, Karolina,Sata?a, Grzegorz
supporting information, (2021/10/29)
Owing to their multifunctional pharmacological profiles (including dual 5-HT1A/5-HT7 action), arylpiperazine derivatives are widely used for treating central nervous system diseases including the depression or neuropathic pain. Herein we describe the design, synthesis and evaluation of biological activity of novel 5-HT7 ligands derived of 2,4,6-triamino-1,3,5-triazine. The studied compounds showed affinity and high selectively towards 5-HT7 receptor with the two most active compounds 34 (Ki = 61 nM), 22 (Ki = 109 nM) showing good metabolic stability and moderate affinity to CYP3A4 isoenzyme. Compound 22 had high hepatotoxicity at a concentration below 50 μM, while compound 34 showed low hepatotoxicity even at a concentration above 50 μM.
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
Compound with dopamine D3 receptor adjusting activity, and applications thereof
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Paragraph 0191; 0196, (2019/03/22)
The invention relates to a compound with dopamine D3 receptor adjusting activity, and applications thereof, and more specifically discloses dopamine receptor D3R as a novel target of post-traumatic stress disorder (PTSD) in prevention, treatment/or auxiliary treatment of PTSD, and screening of anti-PTSD medicines, and relates to applications of a compound with dopamine receptor D3R adjusting activity in preparation of medicines used for preventing, treatment and/or auxiliary treatment of PTSD.
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.
Design, Synthesis, Structure-Activity Relationship Studies, and Three-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Modeling of a Series of O-Biphenyl Carbamates as Dual Modulators of Dopamine D3 Receptor and Fatty Acid Amide Hydrolase
De Simone, Alessio,Russo, Debora,Ruda, Gian Filippo,Micoli, Alessandra,Ferraro, Mariarosaria,Di Martino, Rita Maria Concetta,Ottonello, Giuliana,Summa, Maria,Armirotti, Andrea,Bandiera, Tiziano,Cavalli, Andrea,Bottegoni, Giovanni
, p. 2287 - 2304 (2017/04/03)
We recently reported molecules designed according to the multitarget-directed ligand paradigm to exert combined activity at human fatty acid amide hydrolase (FAAH) and dopamine receptor subtype D3 (D3R). Both targets are relevant for tackling several types of addiction (most notably nicotine addiction) and other compulsive behaviors. Here, we report an SAR exploration of a series of biphenyl-N-[4-[4-(2,3-substituted-phenyl)piperazine-1-yl]alkyl]carbamates, a novel class of molecules that had shown promising activities at the FAAH-D3R target combination in preliminary studies. We have rationalized the structural features conducive to activities at the main targets and investigated activities at two off-targets: dopamine receptor subtype D2 and endocannabinoid receptor CB1. To understand the unexpected affinity for the CB1 receptor, we devised a 3D-QSAR model, which we then prospectively validated. Compound 33 was selected for PK studies because it displayed balanced affinities for the main targets and clear selectivity over the two off-targets. 33 has good stability and oral bioavailability and can cross the blood-brain barrier.
High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice
Boateng, Comfort A.,Bakare, Oluyomi M.,Zhan, Jia,Banala, Ashwini K.,Burzynski, Caitlin,Pommier, Elie,Keck, Thomas M.,Donthamsetti, Prashant,Javitch, Jonathan A.,Rais, Rana,Slusher, Barbara S.,Xi, Zheng-Xiong,Newman, Amy Hauck
, p. 6195 - 6213 (2015/08/24)
The dopamine D3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse, especially
PHENYL CARBAMATES AND THEIR USE AS INHIBITORS OF THE FATTY ACID AMIDE HYDROLASE (FAAH) ENZYME AND MODULATORS OF THE D3 DOPAMINE RECEPTOR (D3DR)
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Page/Page column 33; 37; 38, (2015/02/02)
The invention provides compounds of Formula (I) or pharmaceutically acceptable salts thereof wherein Ar', R1, R2, R3, R4, X, Y are as defined in the description of invention, as multi-target directed ligands (MT
