Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives.

Vernalis (R&D) Ltd, 613 Reading Road, Winnersh, Wokingham RG41 5UA, UK.

Bioorganic & medicinal chemistry letters 2008 May 1

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The (-)-(11R,2'S)-enantiomer of the antimalarial drug mefloquine has been found to be a reasonably potent and moderately selective adenosine A(2A) receptor antagonist. Further investigation of this compound has led to the discovery of a series of keto-aryl thieno[3,2-d]pyrimidine derivatives, which are potent and selective antagonists of the adenosine A(2A) receptor. These derivatives show selectivity against the A(1) receptor. Furthermore, some of these compounds have been shown to have in vivo activity in a commonly used model, suggesting the potential for the treatment of Parkinson's disease.

Citation

Roger J Gillespie, David R Adams, David Bebbington, Karen Benwell, Ian A Cliffe, Claire E Dawson, Colin T Dourish, Allan Fletcher, Suneel Gaur, Paul R Giles, Allan M Jordan, Antony R Knight, Lars J S Knutsen, Anthony Lawrence, Joanne Lerpiniere, Anil Misra, Richard H P Porter, Robert M Pratt, Robin Shepherd, Rebecca Upton, Simon E Ward, Scott M Weiss, Douglas S Williamson. Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives. Bioorganic & medicinal chemistry letters. 2008 May 1;18(9):2916-9