Pharmacological and SAR analysis of the LINS01 compounds at the human histamine H1 , H2 , and H3 receptors
| Autor: | João Paulo S. Fernandes, Álefe Jhonatas Ramos Barbosa, Gustavo A.B. Fernandes, Michelle Fidelis Corrêa, Jillian G. Baker |
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| Rok vydání: | 2018 |
| Předmět: |
Pharmacology
Agonist Nervous system Reporter gene 010405 organic chemistry medicine.drug_class Organic Chemistry Heteroreceptor 01 natural sciences Biochemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry Histamine receptor chemistry.chemical_compound medicine.anatomical_structure chemistry Drug Discovery Autoreceptor medicine Molecular Medicine Receptor Histamine |
| Zdroj: | Chemical Biology & Drug Design. 93:89-95 |
| ISSN: | 1747-0277 |
| Popis: | Histamine is a transmitter that activates the four receptors H1 R to H4 R. The H3 R 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 H3 R over the H4 R. Here, we describe their pharmacological properties at the human H1 R and H2 R in parallel with the H3 R, thus providing a full analysis of these compounds as histamine receptor ligands through reporter gene assays. Eight of the nine LINS01 compounds inhibited H3 R-induced histamine responses, but no inhibition of H2 R-induced responses was seen. Three compounds were weakly able to inhibit H1 R-induced responses. No agonist responses were seen to any of the compounds at any receptor. SAR analysis shows that the N-methyl group improves H3 R affinity while the N-phenyl group is detrimental. The methoxy derivative, LINS01009, had the highest affinity. |
| Databáze: | OpenAIRE |
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