Towards more specific O6-methylguanine-DNA methyltransferase (MGMT) inactivators.
Affiliation
School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland.Issue Date
2011-03-01
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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.Citation
Towards more specific O6-methylguanine-DNA methyltransferase (MGMT) inactivators. 2011, 19 (5):1658-65 Bioorg Med ChemJournal
Bioorganic & Medicinal ChemistryDOI
10.1016/j.bmc.2011.01.038PubMed ID
21320783Type
ArticleLanguage
enISSN
1464-3391ae974a485f413a2113503eed53cd6c53
10.1016/j.bmc.2011.01.038
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