8-Substituted 2-alkynyl-N(9)-propargyladenines as A2A adenosine receptor antagonists.

Abstract:

:Structure-activity relationships of 2-alkynyladenine derivatives were explored by varying substituents at the 9-, 8- and 2-positions of the purine moiety in order to optimize A2A adenosine receptor antagonist activity in vitro. A propargyl group at the 9-position was found to be important for A2A antagonist activity, and the introduction of a halogen, aryl, or heteroaryl at the 8-position further enhanced activity. A series of 8-substituted 2-alkynyl-N(9)-propargyladenine derivatives exhibited potent antagonist activity, with IC50 values in the low nM range. Compound 4a from this series was found to be orally active at a dose of 3 mg/kg in a mouse catalepsy model and a 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

journal_name

Bioorg Med Chem

authors

Endo K,Deguchi K,Matsunaga H,Tomaya K,Yamada K

doi

10.1016/j.bmc.2014.04.041

subject

Has Abstract

pub_date

2014-06-15 00:00:00

pages

3072-82

issue

12

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(14)00306-X

journal_volume

22

pub_type

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