216686-76-9Relevant academic research and scientific papers
Exploring the functionalisation of the thieno[2,3-d]pyrimidinedione core: Late stage access to highly substituted 5-carboxamide-6-aryl scaffolds
O'Rourke, Kerry M.,Johnstone, Erin S.,Becker, Holger M.,Pimlott, Sally L.,Sutherland, Andrew
, p. 4086 - 4094 (2018)
The thieno[2,3-d]pyrimidinedione core is found as a component in a range of pharmaceutically active compounds, however, synthetic approaches to these scaffolds rely on access to functionalised, highly substituted thiophenes. Here we describe a new approach for the preparation of 5-carboxamide-6-aryl analogues that involves a two-step synthesis of the thieno[2,3-d]pyrimidinedione core from a readily available mercaptouracil derivative. Thio-alkylation with ethyl 3-bromopyruvate, followed by cyclisation and dehydration mediated by polyphosphoric acid allowed the scalable synthesis of the thieno[2,3-d]pyrimidinedione unit. The late-stage functionalisation of this core motif via bromination of the thiophene ring and a subsequent Suzuki-Miyaura reaction as the key steps permitted access to a novel library of 5-carboxamide-6-aryl analogues. The physicochemical properties of these compounds were determined, generating an insight into the potential bioavailability of these scaffolds. Based on these results, a selection of the novel 5-carboxamide-6-aryl analogues were tested as lactate uptake inhibitors of monocarboxylate transporters 1, 2 and 4 in Xenopus oocytes.
Thieno[2,3-d]pyrimidine-2,4-diones
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, (2008/06/13)
Compounds of formula (I): wherein R1, R2, and R3are defined in the specification. The compounds are useful for treating or reducing the risk of reversible obstructive airways disease.
