Organic & Biomolecular Chemistry 2006-05-07

The syntheses and properties of tricyclic pyrrolo[2,3-d]pyrimidine analogues of S6-methylthioguanine and O6-methylguanine.

Ana R Hornillo-Araujo, Adam J M Burrell, Miren K Aiertza, Takayuki Shibata, David M Hammond, Dolorès Edmont, Harry Adams, Geoffrey P Margison, David M Williams

Index: Org. Biomol. Chem. 4(9) , 1723-9, (2006)

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Abstract

The syntheses of novel tricyclic pyrrolo[2,3-d]pyrimidine analogues of S6-methylthioguanine are described. The crystal structures and pKa values of these and related O6-methylguanine analogues are reported. All compounds display higher pKa values than O6-methylguanine with the sulfur-containing analogues being the more basic and exhibiting higher stability in aqueous solution. In a standard substrate assay with the human repair protein O6-methylguanine-DNA methyltransferase (MGMT) only the oxygen-containing analogue displayed activity.