22715-33-9Relevant academic research and scientific papers
Imidazopyridine- and purine-thioacetamide derivatives: Potent inhibitors of nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1)
Chang, Lei,Lee, Sang-Yong,Leonczak, Piotr,Rozenski, Jef,De Jonghe, Steven,Hanck, Theodor,Müller, Christa E.,Herdewijn, Piet
, p. 10080 - 10100 (2015/02/05)
Nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) belongs to the family of ecto-nucleotidases, which control extracellular nucleotide, nucleoside, and (di)phosphate levels. To study the (patho)physiological roles of NPP1 potent and selective inhibitors with drug-like properties are required. Therefore, a compound library was screened for NPP1 inhibitors using a colorimetric assay with p-nitrophenyl 5′-thymidine monophosphate (p-Nph-5′-TMP) as an artificial substrate. This led to the discovery of 2-(3H-imidazo[4,5-b]pyridin-2-ylthio)-N-(3,4-dimethoxyphenyl)acetamide (5a) as a hit compound with a Ki value of 217 nM. Subsequent structure-activity relationship studies led to the development of purine and imidazo[4,5-b]pyridine analogues with high inhibitory potency (Ki values of 5.00 nM and 29.6 nM, respectively) when assayed with p-Nph-5′-TMP as a substrate. Surprisingly, the compounds were significantly less potent when tested versus ATP as a substrate, with Ki values in the low micromolar range. A prototypic inhibitor was investigated for its mechanism of inhibition and found to be competitive versus both substrates.
Synthesis and Properties of 7-Alkoxyfurazanopyrimidines and Their Use in the Preparation of 4-Alkoxypteridines and N3-Substituted Pterins
Boyle, Peter H.,Lockhart, Ronan J.
, p. 5127 - 5132 (2007/10/02)
Reaction of 5-amino-7-(methylthio)furazanopyrimidine (4) with a range of alcohols in the presence of bromine leads to the formation of the corresponding 5-amino-7-alkoxyfurazanopyrimidines (5-10).These on hydrogenolysis afford 6-alkoxy-2,4,5-triaminopyrimidines, which can be condensed with benzil to give 2-amino-4-alkoxypteridines (17-21).The product from hydrogenolysis of 5-amino-7-(2-chloroethoxy)furazanopyrimidine (7), however, undergoes intramolecular cyclization to a 2,3-dihydrooxazolopyrimidinium compound (23), which behaves as a heteronuclear resonance stabilized ambident cation.Reaction of it with nucleophiles followed by condensation with benzil leads to N3-substituted pteridines.
