Carboxamide ribonucleosides

Aminoimidazole-4-carboxamide ribonucleoside (also known as AICA riboside or AICAR). An adenosine analogue that is taken up into cells by adenosine transporters and converted by adenosine kinase to the monophosphorylated nucleotide form, ZMP. ZMP is an analogue of AMP that activates the AMP-activated protein kinase (AMPK), for which acadesine or AICAR can be used as a pharmacological activator. 

J.M. CoRTON, J.G. Gillespie, S.A. Hawley, and D.G. Hardie, 5-Aminoimida-zole-4-carboxamide ribonucleoside. A specific method for activating AMP-activat-ing protein kinase in intact cells , Eur. J. Biochem., 1995, 229, 558-565. 

Although procyclic forms of T. brucei gambiense are incapable of de novo synthesis, the last two enzymes of the pathway are present since the intermediate 5-amino-imidazolo-4-carboxamide ribosylphosphate (AICAR) will maintain viability for over 6 weeks (8). Purine base incorporation is qualitatively identical to that found for T. cruzi both trypanosomes lack the adenine deaminase which is found in Leishmania (Fig. 6.7). Purine ribonucleosides were utilized slightly more efficiently than their corresponding purine bases. 

An enantioselective synthesis of carbocyclic tetrazole C-ribonucleosides has been accomplished by first preparing the intermediate (lS,2S,3R,4R)-4-benzoyloxy-methyl-2,3-isopropylidenedioxycyclopentene-l-carbonitrile 1417 from its carboxamide 1416 by dehydration with TFAA in 97% yield. Cyclization of 1417 with azide then gives the tetrazole 1418 [1079]. 

Mercaptonurine - 5-Formamide-l-B-ribofuranosylthioimidazole-4-carboxamide 2, 3, 5 -triformate, is comparable with 6-mercaptopurine (6-MP) for the treatment of leukemias.33 it is cross-resistant with 6-MP. Conversion of 6-MP ribonucleoside to 6-MeMP ribonucleotide has been shown in L-1210 leukemia cells, adenocarcinoma 755 cells, H. Ep. No. 2 cells and other systems. 6-MeMP ribonucleotide is responsible for the inhibition of purine synthesis produced by 6-MP.3 Metabolism of 6-MeMP in Ehrlich ascites cells has been studied.Breakdown of the active nucleotide form of the 6-thlopurines by alkaline phosphohydrolase is probably responsible... 

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