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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Profiling of LINS01 compounds at human dopamine D-2 and D-3 receptors

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Correa, Michelle F. [1] ; Reiner, David [2] ; Fernandes, Gustavo A. B. [1] ; Varela, Marina T. [1] ; Aranha, Cecilia M. S. Q. [1] ; Stark, Holger [2] ; Fernandes, Joao Paulo S. [1]
Total Authors: 7
[1] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Rua Sao Nicolau 210, BR-09913030 Diadema, SP - Brazil
[2] Heinrich Heine Univ Dusseldorf, Inst Pharmaceut & Med Chem, Univ Str 1, D-40225 Dusseldorf - Germany
Total Affiliations: 2
Document type: Journal article
Source: JOURNAL OF CHEMICAL SCIENCES; v. 132, n. 1 DEC 2019.
Web of Science Citations: 0

Histamine and dopamine neuronal pathways display interesting overlapping in the CNS, especially in the limbic areas, making them very attractive to designing drugs with synergistic and/or additive effects. The roles of these systems to treat schizophrenia, drug addiction, Parkinson's and Alzheimer's diseases, among others are widely known. The LINS01 compounds were previously reported as histamine H-3 receptor (H3R) antagonists and some of them are under evaluation in rodent memory models. Considering their pharmacological potential and similarities to literature dopamine D-2 receptor (D2R) and dopamine D-3 receptor (D3R) ligands, this work aimed to evaluate these compounds as ligands these receptors by using {[}H-3]spiperone displacement assays. A set of 11 compounds containing the dihydrobenzofuranyl-piperazine core with substituents at 5-position of dihydrobenzofuran ring and at the piperazine nitrogen was examined. The compounds showed low to moderate affinities at both, D2R and D3R. N-Phenyl compounds LINS01005 (1d), LINS01011 (1h), LINS01012 (1i) and LINS01016 (1k) showed the highest affinities in the set to D3R (K-i 0.3-1.5 mu M), indicating that N-phenylpiperazine moiety increases the affinity to this receptor subtype with some selectivity, since they showed lower affinities to D2R (K-i 1.3-5.5 mu M). With the LINS01 compounds showing moderate binding affinity, new lead structures for optimization with regards to combined H3R and D2R/D3R-ligands are provided. (AU)

FAPESP's process: 17/05441-6 - Dihydrobenzofuranyl-phenylpiperazines as vasodilating agents: synthesis and evaluation of LINS01005 analogs
Grantee:Gustavo Ariel Borges Fernandes
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/03918-2 - Evaluation of the antiparasitic activity and cytotoxicity of natural products derivatives in Trypanosoma cruzi: design and synthesis of analogues potentially superior
Grantee:Marina Themoteo Varela
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 18/04488-1 - Histaminergic and dopaminergic ligands as procognitive agents: synthesis and evaluation of aryloxyalkylpiperazines
Grantee:Cecília Maria Simões de Queiroz Aranha
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/25028-3 - Antihistamines H3R/H4R as procognitive agents: a multitarget approach
Grantee:João Paulo dos Santos Fernandes
Support Opportunities: Regular Research Grants