Synthesis and preliminary pharmacological characterisation of a new class of nitrogen-containing bisphosphonates (N-BPs).
Bioorg Med Chem
; 18(7): 2428-38, 2010 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-20299227
A new series of bisphosphonates bearing either the nitrogen-containing NO-donor furoxan (1,2,5-oxadiazole 2-oxide) system or the related furazan (1,2,5-oxadiazole) in lateral chain has been developed. pK(a) values and affinity for hydroxyapatite were determined for all the compounds. The products were able to inhibit osteoclastogenesis on RAW 246.7 cells at 10microM concentration. The most active compounds were further assayed on human PBMC cells and on rat microsomes. Unlike most nitrogen-containing bisphosphonates which target farnesyl pyrophosphate synthase, experimental and theoretical investigations suggest that the activity of our derivatives may be related to different mechanisms. The furoxan derivatives were also tested for their ability to relax rat aorta strips in view of their potential NO-dependent vasodilator properties.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Difosfonatos
/
Conservadores da Densidade Óssea
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Nitrogênio
Limite:
Animals
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Humans
/
Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article