Synthesis of 3-(carboxyarylalkyl)imidazo[2,1-f][1,2,4]triazines as potential inhibitors of AMP deaminase.
C-Ribosyl 1,2,4-triazolo[1,2,4]triazines which are able to undergo covalent hydration are of interest as potential inhibitors of AMP deaminase. In a search for compounds with improved bioavailability we have synthesized compounds in which the sugar has been replaced by carboxyarylalkyl based ribose phosphate mimics. The target carboxyarylalkyl imidazotriazines 11 and 12 were synthesized using a linear seven step sequence starting from simple benzoate derivatives. Alternatively, the hydroxyethyl imidazotriazine 39 is available in five steps and this synthon was used to prepare the imidazotriazines 34 and 48 in a short convergent manner.
Kirkman
Joseph K
JK
Department of Chemistry, School of Biological and Chemical Sciences, University of Exeter, Stocker Road, Exeter, EX4 4QD, UK.
Lindell
Stephen D
SD
Maechling
Simon
S
Slawin
Alexandra M Z
AM
Moody
Christopher J
CJ
D000659:AMP Deaminase / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000737:chemistry*; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007093:Imidazoles; D014227:Triazines; D000659:AMP Deaminase