606964-84-5Relevant academic research and scientific papers
The synthesis of 7-deazaguanines as potential inhibitors of guanosine triphosphate cyclohydrolase I
Gibson, Colin L.,La Rosa, Salvatore,Ohta, Kyuji,Boyle, Peter H.,Leurquin, Fabien,Lema?on, Alexandra,Suckling, Colin J.
, p. 943 - 959 (2004)
Variously substituted 7-deazaguanines are of interest as inhibitors of GTP cyclohydrolase I, the first enzyme in the biosynthetic pathway leading to dihydrofolate and tetrahydrobiopterin. Methods are described for the synthesis of 7-deazaguanines substituted at positions 2, 6 and 9 (purine numbering) such that a wide diversity of compounds can be prepared. These methods supplement our previous work that established routes for the synthesis of 7- and 8-substituted 7-deazaguanines. Emphasis is placed on the properties of 2-thioalkyl pyrimidines as intermediates because they provide the basis for a traceless solid-state synthesis of purines, pteridines, and their analogues. Compounds prepared have been assessed in a primary screen for their ability to inhibit GTPCH I and 8-methyldeazaguanine has been shown to be significantly more potent than any inhibitor yet described. Several compounds appeared to undergo transformation by GTPCH I; with the aid of a model reaction, their behaviour can be interpreted in the context of the mechanism of the hydrolytic phase of GTPCH I.
A prototype solid phase synthesis of pteridines and related heterocyclic compounds
Gibson, Colin L.,La Rosa, Salvatore,Suckling, Colin J.
, p. 1909 - 1918 (2007/10/03)
The development of a versatile solid phase synthesis of bicyclic polyaza heterocycles including pteridines, purines, and deazapurines is described. The strategy comprises the linking of a pre-formed pyrimidine through a thioether at the 2 or 4 position to a polystyrene resin, the cyclisation of the second ring, and the direct or oxidative cleavage of the product from the resin by nucleophilic substitution. This provides not only for substituent variation in the second ring, but also for variation at the site of cleavage. Limitations in the scope of the methodology are set by the intrinsic reactivity of pyrimidinyl 2- or 4-thioethers which, whilst undergoing ready nitration at C5, are surprisingly difficult to alkylate and acylate.
