Basic Information
ID: ALA1681736
Journal: Bioorg Med Chem
Title: Towards more specific O6-methylguanine-DNA methyltransferase (MGMT) inactivators.
Authors: Lopez S, Margison GP, McElhinney RS, Cordeiro A, McMurry TB, Rozas I.
Abstract: Searching for a novel family of inactivators of the human DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) which is known to bind to the DNA minor groove, we have computationally modelled and synthesised two series of 2-amino-6-aryloxy-5-nitropyrimidines with morpholino or aminodiaryl substituents (potential minor groove binders) at the 4-position. Synthesis of these compounds was achieved by successive substitution of each of the two Cl atoms of 2-amino-4,6-dichloro-5-nitropyrimidine by the corresponding amino and aryloxy derivatives. Biochemical evaluation of these compounds as MGMT inactivators showed poor activities, but in general the 4-bromothenyloxy derivatives showed better inactivation than the benzyloxy versions. DNA binding assessment was not possible due to insolubility problems.
CiteXplore: 21320783
DOI: 10.1016/j.bmc.2011.01.038
Patent ID: ┄
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