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Controlled stepwise conversion of 2,4,6,8-tetrachloropyrimido-[5,4-d ]pyrimidine into 2,4,6,8-tetrasubstituted pyrimido[5,4-d]pyrimidines

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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Abstract

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.


Publication metadata

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

Year: 2002

Volume: 2

Issue: 1

Pages: 108-115

Print publication date: 01/01/2002

ISSN (print): 1472-7781

ISSN (electronic): 1364-5463

Publisher: Royal Society of Chemistry

URL: http://dx.doi.org/10.1039/b102224p

DOI: 10.1039/b102224p


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