Selective adenosine A 2A receptor antagonists
In the early 1990s it became clear that the A 2A adenosine receptor had characteristics that made it distinct from the other A 1, A 2B and A 3 adenosine receptors. Great progress has been made with the discovery of selective A 2A receptor antagonists. A variety of synthetic substitutions on the xant...
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Published in | Farmaco (Società chimica italiana : 1989) Vol. 56; no. 1; pp. 87 - 90 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier SAS
2001
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Subjects | |
Online Access | Get full text |
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Summary: | In the early 1990s it became clear that the A
2A adenosine receptor had characteristics that made it distinct from the other A
1, A
2B and A
3 adenosine receptors. Great progress has been made with the discovery of selective A
2A receptor antagonists. A variety of synthetic substitutions on the xanthine moiety led the chemists of Kyowa–Hakko to discover that introduction of the styryl group in the 8 position of xanthines was critical in achieving compounds endowed with selective A
2A receptor antagonistic properties. One compound, KW 6002, (
E)1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methylxanthine, is currently being developed for treatment of Parkinson's disease. A number of non-xanthine heterocycles have also been synthesized starting from the non-selective adenosine antagonist CGS 15943, a triazoloquinazoline. Thus, replacement of the phenyl ring of CGS 15943 with a heterocyclic ring such as pyrazole or imidazole, led to a series of interesting compounds whose prototype, SCH 58261, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo[4,3-
e]-1,2,4-triazolo[1,5-
c]pyrimidine, has become a reference A
2A receptor antagonist. Modification of N7 substituents has progressed to optimize A
2A receptor selectivity and pharmacokinetic characteristics. A related class of compounds having a bicyclic instead of the tricyclic ring structure is also of interest. The prototype of these triazintriazolo derivatives, ZM 241385, is a potent A
2A receptor antagonist; however, it also shows interactions with A
2B receptors. The relevance of the A
2A receptors in specific disease states, especially in the central nervous system, makes this class of adenosine receptor blockers of interest for treatment of neurodegenerative disorders such as Parkinson's disease. |
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ISSN: | 0014-827X 1879-0569 |
DOI: | 10.1016/S0014-827X(01)01024-2 |