Lookup NU author(s): Dr Julian Scott Northen,
Emeritus Professor Bill Clegg,
Professor Nicola Curtin,
Professor Roger Griffin,
Professor Bernard Golding
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For the rational synthesis of 2,4,6,8-tetrasubstituted pyrimido[5,4-d]pyrimidines, required as purine mimetics, sequential nucleophilic substitutions of 2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine have been investigated. Reaction conditions have been devised leading to 2,4,6,8-tetrasubstituted pyrimido[5,4-d]pyrimidines with patterns of substitution denoted as abab (reaction with nucleophile 1 at C-4 and C-8, followed by nucleophile 2 at C-2 and C-6) or abac (reaction with nucleophile 1 at C-4 and C-8, nucleophile 2 at C-2 and nucleophile 3 at C-6) or abcd (reaction with nucleophile 1 at C-4, nucleophile 2 at C-8, nucleophile 3 at C-2 and nucleophile 4 at C-6). The use of low temperature, relatively dilute solution and careful addition of the amine nucleophile can control the critical first step. The third step in the production of the abcd pattern leads to two regioisomers, which have been structurally characterised by 1H NMR and a crystal structure analysis. Selected 2,4,6,8-tetrasubstituted pyrimido[5,4-d]pyrimidines were tested as inhibitors of the cyclin-dependent kinase 1 complex (cyclin B/CDK1), but none of the compounds showed significant activity.
Author(s): Northen J, Boyle F, Clegg W, Curtin NJ, Edwards A, Griffin R, Golding B
Publication type: Article
Publication status: Published
Journal: Journal of the Chemical Society. Perkin Transactions 1
Print publication date: 01/01/2002
ISSN (print): 1472-7781
ISSN (electronic): 1364-5463
Publisher: Royal Society of Chemistry
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