- Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
-
The present invention relates to substituted xanthines of general formula wherein R1 to R4 are defined as in claim 1, the tautomers and the stereoisomers thereof, mixtures thereof, the prodrugs and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).
- -
-
-
- Purines. XLIX. Synthesis and proton nuclear magnetic resonance study of 3,7-dialkylxanthines and 1,3,7-trialkylxanthines
-
A general synthetic route to 3,7-dialkylxanthines (type 9) from 3,7-dialkyladenines (6) [hence from 3- or 7-alkyladenines (11 or 10)] has been established. The route started with ethoxycarbonylation of 1-alkyl-4-(alkylamino)1H-imidazole-5-carboxamides (7), readily obtainable from 6 by alkaline hydrolysis, and proceeded through cyclization of the resulting carbamates (8) under alkaline conditions. Alkylation of 9 with alkyl halide in N,N-dimethylformamide in the presence of anhydrous K2CO3 extended the above synthetic route to the 1,3,7-trialkylxanthine level (type 14). Hydrogenolytic deb nzylation of 3-benzyl-1,7-dimethylxanthine (16), prepared by following this general synthetic route, furnished paraxanthine (26) in fair yield. Conversion of 26 into 3-(4-hydroxy-3-nitrobenzyl)-1,7-dimethylxanthine (24), isomeric with the bryozoan purine phidolopin (2), was effected through aralkylation with 4-(methoxymethoxy)-3-nitrobenzyl bromide (28) followed by O-deprotection. On the basis of proton nuclear magnetic resonance data for the 3,7-dialkylxanthines (3 and 9b-i) and 1,3,7-trialkylxanthines (5 and 14-22) thus prepared, reliable criteria for distinguishing signals of N-alkyl substituents at various positions are put forward.
- Fujii,Saito,Tamura
-
p. 2855 - 2862
(2007/10/02)
-