Scouting human A(3) adenosine receptor antagonist binding mode using a molecular simplification approach: From triazoloquinoxaline to a pyrimidine skeleton as a key study
The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, has been applied to design new classes of human A(3) adenosine receptor (AR) antagonists. Over the past decade, we have focused a part o...
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Published in | Journal of medicinal chemistry Vol. 50; no. 26; pp. 6596 - 6606 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
Amer Chemical Soc
27.12.2007
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Subjects | |
Online Access | Get full text |
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Summary: | The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, has been applied to design new classes of human A(3) adenosine receptor (AR) antagonists. Over the past decade, we have focused a part of our research on the study of AR antagonists belonging to strictly correlated classes of tricyclic compounds. One of these classes is represented by the 2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives, either 4-amino or 4-oxosubstituted, which were intensively investigated by evaluating the effect of different substituents on the 2-phenyl ring and on the 4-amino group. Using an in silico molecular simplification approach, a new series of easily synthesizable 2-amino/2-oxoquinazoline-4-carboxamido derivatives have been discovered, presenting high affinity and selectivity against human A(3) AR. |
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ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/jm070852a |