RESUMO
Racemic 2-O-[4'(9''-N-purinyl)butyl] myo-inositol 1,4,5-tris(phosphate) 8 was synthesized starting from myo-inositol. Substitution of position 2 by an alkyl side chain was rendered possible by inversion of the chair conformation of the inositol ring by means of an orthoester. The final compound is a full agonist with the same order of potency as d-myo-inositol 1,4,5-tris(phosphate).
Assuntos
Inositol 1,4,5-Trifosfato/análogos & derivados , Inositol 1,4,5-Trifosfato/síntese química , Inositol 1,4,5-Trifosfato/metabolismo , Purinas/síntese química , Receptores Citoplasmáticos e Nucleares/agonistas , Córtex Suprarrenal/ultraestrutura , Animais , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Bovinos , Linhagem Celular , Retículo Endoplasmático/metabolismo , Técnicas In Vitro , Inositol 1,4,5-Trifosfato/química , Inositol 1,4,5-Trifosfato/farmacologia , Receptores de Inositol 1,4,5-Trifosfato , Microssomos/efeitos dos fármacos , Microssomos/metabolismo , Conformação Molecular , Pâncreas/citologia , Permeabilidade , Purinas/química , Purinas/farmacologia , Ensaio Radioligante , Receptores Citoplasmáticos e Nucleares/metabolismo , EstereoisomerismoRESUMO
Cyclopentanic analogues of myo-inositol 1,4,5-tris(phosphate) were synthesised starting from cyclopentadiene. The affinities of the trisphosphorylated derivatives for the Ins(1,4,5)P(3) receptors were equipotent to that of compound 4, showing that the relative orientation of the functional groups, particularly of the hydroxyl, is not of prime importance in this series. The (31)P NMR titration curves show that the tris(phosphate) 5 behaves as the superimposition of an independent phosphate and a vicinal bis(phosphate).
