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

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Gillespie RJ, Adams DR, Bebbington D, Benwell K, Cliffe IA, Dawson CE, Dourish CT, Fletcher A, Gaur S, Giles PR, Jordan AM, Knight AR, Knutsen LJ, Lawrence A, Lerpiniere J, Misra A, Porter RH, Pratt RM, Shepherd R, Upton R, Ward SE, Weiss SM, Williamson DS

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

Bioorg Med Chem Lett. 2008 May 1;18(9):2916-9. doi: 10.1016/j.bmcl.2008.03.075. Epub 2008 Mar 30.

PubMed ID

18406614 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drugs

Mefloquine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Mefloquine	Adenosine receptor A2a	Protein	Humans	Unknown	Antagonist	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Mefloquine	Adenosine receptor A2a	Ki (nM)	61	N/A	N/A	Details
Mefloquine	Adenosine receptor A2a	Ki (nM)	2534	N/A	N/A	Details
Mefloquine	Adenosine receptor A2a	Ki (nM)	124	N/A	N/A	Details
Mefloquine	Adenosine receptor A2a	Ki (nM)	6553	N/A	N/A	Details