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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.)

Pharmacological and SAR analysis of the LINS01 compounds at the human histamine H-1, H-2, and H-3 receptors

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Correa, Michelle Fidelis [1] ; Ramos Barbosa, Alefe Jhonatas [1] ; Borges Fernandes, Gustavo Ariel [1] ; Baker, Jillian G. [2] ; dos Santos Fernandes, Joao Paulo [1]
Total Authors: 5
[1] Univ Fed Sao Paulo, Dept Ciencias Farmaceut, Diadema - Brazil
[2] Univ Nottingham, Sch Life Sci, Cell Signalling Res Grp, Nottingham - England
Total Affiliations: 2
Document type: Journal article
Source: CHEMICAL BIOLOGY & DRUG DESIGN; v. 93, n. 1, p. 89-95, JAN 2019.
Web of Science Citations: 2

Histamine is a transmitter that activates the four receptors H1R to H4R. The H3R is found in the nervous system as an autoreceptor and heteroreceptor, and controls the release of neurotransmitters, making it a potential drug target for neuropsychiatric conditions. We have previously reported that the 1-(2,3-dihydro-1-benzofuran-2-yl)methylpiperazines (LINS01 compounds) have the selectivity for the H3R over the H4R. Here, we describe their pharmacological properties at the human H1R and H2R in parallel with the H3R, thus providing a full analysis of these compounds as histamine receptor ligands through reporter gene assays. Eight of the nine LINS01 compounds inhibited H3R-induced histamine responses, but no inhibition of H2R-induced responses was seen. Three compounds were weakly able to inhibit H1R-induced responses. No agonist responses were seen to any of the compounds at any receptor. SAR analysis shows that the N-methyl group improves H3R affinity while the N-phenyl group is detrimental. The methoxy derivative, LINS01009, had the highest affinity. (AU)

FAPESP's process: 16/23139-2 - Synthesis and biological evaluation of the LINS01 series as procognitive agents: a multitarget approach
Grantee:Michelle Fidelis Corrêa
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 16/25028-3 - Antihistamines H3R/H4R as procognitive agents: a multitarget approach
Grantee:João Paulo dos Santos Fernandes
Support type: Regular Research Grants
FAPESP's process: 17/05441-6 - Dihydrobenzofuranyl-phenylpiperazines as vasodilating agents: synthesis and evaluation of LINS01005 analogs
Grantee:Gustavo Ariel Borges Fernandes
Support type: Scholarships in Brazil - Scientific Initiation