These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Synthesis and evaluation of 5-amino-1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine and certain related nucleosides as inhibitors of purine nucleoside phosphorylase.
    Author: Sanghvi YS, Hanna NB, Larson SB, Fujitaki JM, Willis RC, Smith RA, Robins RK, Revankar GR.
    Journal: J Med Chem; 1988 Feb; 31(2):330-5. PubMed ID: 3123692.
    Abstract:
    The 5-amino and certain related derivatives of the powerful purine nucleoside phosphorylase (PNPase) inhibitor 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine (TCNR,3) have been prepared and evaluated for their PNPase activity. Acetylation followed by dehydration of 5-chloro-1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (4a) gave 5-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1,2,4-triazole-3- carbonitrile (5). Ammonolysis of 5 furnished 5-amino-1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine (5-amino-TCNR, 6), the structure of which was assigned by single-crystal X-ray analysis. Acid-catalyzed fusion of methyl 5-chloro-1,2,4-triazole-3-carboxylate (7a) with 5-deoxy-1,2,3-tri-O-acetyl-D-ribofuranose (8) gave methyl 5-chloro-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)- 1,2,4-triazole-3-carboxylate (9a) and the corresponding positional isomer 9b. Transformation of the functional groups in 9a afforded a route to 5'-deoxyribavirin (9i). Compound 9a was converted in four steps to 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)-1,2,4-triazole-3- carboxamidine (5'-deoxy-5-amino-TCNR, 9g). Similar acid-catalyzed fusion of 1,2,4-triazole-3-carbonitrile (7b) with 8 and ammonolysis of the reaction product 9h gave yet another route to 9i. Treatment of 9h with NH3/NH4Cl furnished 1-(5-deoxy-beta-D-ribofuranosyl)- 1,2,4-triazole-3-carboxamidine (5'-deoxy-TCNR, 9k). The C-nucleoside congener of TCNR (3-beta-D-ribofuranosyl- 1,2,4-triazole-5-carboxamidine, 12) was prepared in two steps from 3-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)- 1,2,4-triazole-5-carbonitrile (10) by conventional procedure. 5-Amino-TCNR (6) displayed a more potent, high-affinity inhibition than TCNR, with a Ki of 10 microM. In contrast, 5'-deoxy-5-amino-TCNR (9g) was a significantly less potent inhibitor of PNPase, compared to 5'-deoxy-TCNR (Ki = 80 and 20 microM, respectively). Neither the C-nucleoside congener of TCNR (12) nor that of ribavirin were found to inhibit inosine phosphorolysis.
    [Abstract] [Full Text] [Related] [New Search]