C-glycoside based mimics of D-myo-inositol 1,4,5-trisphosphate.
Epimeric C-glycoside based polyphosphates, alpha- and beta-D-glucopyranosylmethanol 3,4,1'-trisphosphates (8 and 9) were prepared from D-glucose. The key intermediate, allyl 2,6-di-O-benzyl-alpha-D-glucopyranoside, was prepared in five steps (67% yield) from allyl alpha-D-glucopyranoside without the need for chromatography. Compounds 8 and 9 were shown to be full agonists at the Ins(1,4,5)P3 receptors of permeabilised hepatocytes, but with markedly different potencies. Such C-glycoside analogues are worthy of further development as Ins(1,4,5)P, receptor ligands.
Rosenberg
H J
HJ
Department of Pharmacy and Pharmacology, University of Bath, UK.
Riley
A M
AM
Correa
V
V
Taylor
C W
CW
Potter
B V
BV
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002132:Calcium Radioisotopes; D020013:Calcium Signaling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000737:chemistry; D006027:Glycosides / Q000737:chemistry*; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018716:Molecular Mimicry; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D006027:Glycosides; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C085029:adenophostin A; C085030:adenophostin B; D015544:Inositol 1,4,5-Trisphosphate; D005947:Glucose; D000241:Adenosine; D002118:Calcium