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Review
. 2011 Oct 19;2(10):555-67.
doi: 10.1021/cn2000537. Epub 2011 Jun 21.

Adenosine A(2A) Receptor Antagonists and Parkinson's Disease

Brian C Shook  1 , Paul F Jackson
Affiliations
Review

Adenosine A(2A) Receptor Antagonists and Parkinson's Disease

Brian C Shook et al. ACS Chem Neurosci. .

Abstract

This Review summarizes and updates the work on adenosine A(2A) receptor antagonists for Parkinson's disease from 2006 to the present. There have been numerous publications, patent applications, and press releases within this time frame that highlight new medicinal chemistry approaches to this attractive and promising target to treat Parkinson's disease. The Review is broken down by scaffold type and will discuss the efforts to optimize particular scaffolds for activity, pharmacokinetics, and other drug discovery parameters. The majority of approaches focus on preparing selective A(2A) antagonists, but a few approaches to dual A(2A)/A(1) antagonists will also be highlighted. The in vivo profiles of compounds will be highlighted and discussed to compare activities across different chemical series. A clinical report and update will be given on compounds that have entered clinical trials.

Keywords: 6-OHDA; A1 receptor antagonist; A2A receptor antagonist; Adenosine; MPTP; Parkinson’s disease; catalepsy.

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Figures

Figure 1
Figure 1
Xanthine based A2A antagonists.
Figure 2
Figure 2
Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines.
Figure 3
Figure 3
Aryl piperazine substituted pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines.
Figure 4
Figure 4
Fused heterocyclic substituted pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines.
Figure 5
Figure 5
Aryl piperazine substituted 3H-[1,2,4]-triazolo[5,1-i]purin-5-amines.
Figure 6
Figure 6
Arylindenopyrimidines.
Figure 7
Figure 7
Substituted arylindenopyrimidines.
Figure 8
Figure 8
Pyrazolo[4,3-e]-1,2,4-trizolo[4,3-c]pyrimidon-3-one and thiazolotriazolopyrimidines.
Figure 9
Figure 9
Substituted 1,2,4-triazolo[1,5-c]pyrimidines.
Figure 10
Figure 10
Substituted purinones.
Figure 11
Figure 11
Thieno[3,2-d]pyrimidines, pyrazolo[3,4-d]pyrimidines, and 6-arylpurines.
Figure 12
Figure 12
Benzyl substituted triazolo[4,5-d]pyrimidines.
Figure 13
Figure 13
Triazolo-9H-purines.
Figure 14
Figure 14
Aminomethyl substituted thieno[2,3-d]pyrimidines.
Figure 15
Figure 15
2-Aminoimidazopyridines.
Figure 16
Figure 16
Substituted 4-morpholino-benzothiazoles.
Figure 17
Figure 17
4-Aryl and 4-morpholino substituted benzofurans.
Figure 18
Figure 18
Pyridone substituted pyrazines.
Figure 19
Figure 19
Heterocyclic substituted 2-amino-thiazoles.
Figure 20
Figure 20
Various trisubstituted pyrimidines.
Figure 21
Figure 21
Piperazine substituted pyrimidine acetamides.
Figure 22
Figure 22
Acylaminopyrimidines.
Figure 23
Figure 23
Pyrimidine, pyridine, and triazine carboxamides.
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