84602-82-4Relevant articles and documents
Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors
Laufer, Stefan A.,Domeyer, David M.,Scior, Thomas R. F.,Albrecht, Wolfgang,Hauser, Dominik R. J.
, p. 710 - 722 (2007/10/03)
On the basis of ATP adenine, a series of adenine and purine derivatives was prepared and tested for their ability to inhibit a spectrum of disease-related kinases. There has been scant research investigating the potential of cosubstrate derived kinase inhibitors for other kinases than CDKs. Our inhibitor design combined the purine system from the original cosubstrate ATP and phenyl moieties in order to explore possible interactions with the different regions of the ATP binding site in several disease-related protein kinases. There have been a number of hits for the assayed substances, which led us to conclude that the spectrum of compounds may prove to be a valuable tool kit for the evaluation of bonding and selectivity patterns for a wide variety of kinases.
Anion Formation and Ring Opening of 9-Substituted Purines in Liquid Ammonia Containing Potassium Amide
Kos, Nico J.,Plas, Henk C. van der,Blees, Wouter J. F.
, p. 850 - 855 (2007/10/02)
Reaction of 9-methylpurine, 6-chloro-9-methylpurine, and 2',3'-O-isopropylidenenebularine with potassium amide in liquid ammonia leads to opening of the imidazole ring, yielding, after hydrolysis during the workup, 4-(substituted amino)-5-formamidopyrimidines. 6-Chloro-9-methylpurine gives, besides 6-chloro-4-(methylamino)-5-formamidopyrimidine as main product, small amounts of 9-methyladenine and 6-chloro-7,8-dihydro-8-oxo-9-methylpurine.The ring opening will involve adduct formation at position 8.Nebularine, adenosine, and 2',3'-O-isopropylideneadenosine do not react .With a greater excess of potassium amide 2',3'-O-isopropylideneadenosine loses the sugar moiety.The existence of an anion at position 8 can be proved in 9-methylpurine via scavenging with bromobenzene in liquid ammonia containing potassium amide, yielding the 8-phenyl derivative.With 6-chloro-9-(2-tetrahydropyranyl)purine this reaction gives 6-anilino-9-(2-tetrahydropyranyl)purine.Scavenging of 9-methyladenine with bromobenzene gives 6-anilino-9-methylpurine. 1H and 13C NMR spectroscopy confirm that in this strongly basic medium 7- and 9-methyladenine and 6-(methylamino)-9-methylpurine deprotonate at C-8 and lose a proton from the amino group.Both 8-(methylthio)- and 8-amino-9-methylpurine give with potassium amide in liquid ammonia opening of the imidazole ring, yielding 5-(cyanoamino)-4-(methylamino)pyrimidine, which can react further to give either 8-amino-9-methylpurine or 7,8-dihydro-8-oxo-9-methylpurine.
