Bicyclic analogues of D-myo-inositol 1,4,5-trisphosphate related to adenophostin A: synthesis and biological activity.
J Med Chem
; 44(13): 2108-17, 2001 Jun 21.
Article
en En
| MEDLINE
| ID: mdl-11405648
ABSTRACT
The high affinity of adenophostin A for 1D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] receptors may be related to an alteration in the position of its 2'-phosphate group relative to the corresponding 1-phosphate group in Ins(1,4,5)P(3). To investigate this possibility, two bicyclic trisphosphates 9 and 10, designed to explore the effect of relocating the 1-phosphate group of Ins(1,4,5)P(3) using a novel fused-ring system, were synthesized from myo-inositol. Biological evaluation of 9 and 10 at the Ins(1,4,5)P(3) receptors of hepatocytes showed that both were recognized by hepatic Ins(1,4,5)P(3) receptors and both stimulated release of Ca(2+) from intracellular stores, but they had lower affinity than Ins(1,4,5)P(3). This finding may be explained by considering the three-dimensional structures of 9 and 10 in light of recent studies on the conformation of adenophostin A.
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Bases de datos:
MEDLINE
Asunto principal:
Agonistas de los Canales de Calcio
/
Inositol 1,4,5-Trifosfato
/
Adenosina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2001
Tipo del documento:
Article
País de afiliación:
Reino Unido