Synthesis of (+/-)-2-O-[4'-(N-9''-purinyl)butyl] myo-inositol 1,4,5-tris(phosphate), a potent full agonist at the D-myo-inositol 1,4,5-tris(phosphate) receptor.
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).
Moris
Marc-Antoine
MA
Laboratoire de Pharmacochimie de la Communication Cellulaire UMR 7081 du CNRS, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, 74, route du Rhin, 67401 Illkirch, France.
Caron
Annabelle Z
AZ
Guillemette
Gaétan
G
Rognan
Didier
D
Schmitt
Martine
M
Schlewer
Gilbert
G
D000302:Adrenal Cortex / Q000648:ultrastructure; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008968:Molecular Conformation; D010179:Pancreas / Q000166:cytology; D010539:Permeability; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D013237:Stereoisomerism
C498578:2-O-(4'-(N-9''-purinyl)butyl) myo-inositol 1,4,5-tris(phosphate); D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011687:Purines; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium