Design and evaluation of dihydroxytetrahydro-1H-pyrrolo[2,1-c]- [1,4]benzothiazines as conformationally restricted transition-state inhibitors of beta-ribosidases.
[structure: see text] The preparation of three new chiral thiazines from ribose is described. Two of these are dihydroxytetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazines with iminopentitol substructures corresponding to the L-lyxo and D-ribo configurations. They were designed to present a favorable transition-state mimic for the inhibition of ribosidases. This new thiazine class opens the way to the development of new inhibitors to carbohydrate processing enzymes of therapeutic importance such as nucleoside hydrolases and purine nucleoside phosphorylases.
Gao
Li
L
Department of Chemistry, Michigan State University, East Lansing, 48824, USA.
Hollingsworth
Rawle I
RI
D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006859:Hydrogen / Q000737:chemistry*; D006900:Hydroxylation; D008958:Models, Molecular; D008968:Molecular Conformation; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013843:Thiazines / Q000138:chemical synthesis* / Q000737:chemistry
C446962:1,4-benzothiazine; D004791:Enzyme Inhibitors; D013843:Thiazines; D006859:Hydrogen; D011683:Purine-Nucleoside Phosphorylase; D009699:N-Glycosyl Hydrolases