1-[(2,3-Dihydro-1-benzofuran-2-yl) methyl]piperazines as novel anti-inflammatory compounds: Synthesis and evaluation on H3 R/H4 R.
Chem Biol Drug Des
; 90(2): 317-322, 2017 08.
Article
em En
| MEDLINE
| ID: mdl-28109127
ABSTRACT
The histamine receptors (HRs) are members of G-protein-coupled receptor superfamily and traditional targets of huge therapeutic interests. Recently, H3 R and H4 R have been explored as targets for drug discovery, including in the search for dual-acting H3 R/H4 R ligands. The H4 R, the most recent histamine receptor, is a promising target for novel anti-inflammatory agents in several conditions such as asthma and other chronic inflammatory diseases. Due to similarity with previously reported ligands of HRs, a set of 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines were synthesized and evaluated in competitive binding assays as H3 R/H4 R ligands herein. The results showed the compounds presented affinity (Ki ) for H3 R/H4 R in micromolar range, and they are more selective to H3 R. All the compounds showed no important cytotoxicity to mammalian cells. The phenyl-substituted compound LINS01005 has shown the higher affinity of the set for H4 R, but no considerable selectivity toward this receptor over H3 R. LINS01005 showed interesting anti-inflammatory activity in murine asthma model, reducing the eosinophil counts in bronchoalveolar lavage fluid, as well as the COX-2 expression. The presented compounds are valuable prototypes for further improvements to achieve better anti-inflammatory agents.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
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Receptores Histamínicos
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Receptores Histamínicos H3
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Receptores Acoplados a Proteínas G
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Anti-Inflamatórios
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Chem Biol Drug Des
Assunto da revista:
BIOQUIMICA
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FARMACIA
/
FARMACOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Brasil