115338-24-4Relevant articles and documents
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
, (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.
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
supporting information, 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.
Synthesis and biological characterization of novel hybrid 7-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro- naphthalen-2-ol and their heterocyclic bioisosteric analogues for dopamine D2 and D3 receptors
Dutta, Aloke K.,Venkataraman, Sylesh K.,Fei, Xiang-Shu,Kolhatkar, Rohit,Zhang, Shijun,Reith, Maarten E.A.
, p. 4361 - 4373 (2007/10/03)
In a recent preliminary communication we described the development of a series of hybrid molecules for the dopamine D2 and D3 receptor subtypes. The design of these compounds was based on combining pharmacophoric elements of aminotetralin and piperazine m
