T. Gungor et al., N6-SUBSTITUTED ADENOSINE RECEPTOR AGONISTS - SYNTHESIS AND PHARMACOLOGICAL ACTIVITY AS POTENT ANTINOCICEPTIVE AGENTS, Journal of medicinal chemistry, 37(25), 1994, pp. 4307-4316
Novel N-6-(indol-3-yl)alkyl derivatives of adenosine were synthesized.
The adenosine receptor affinity and the antinociceptive activity of t
hese compounds were assessed in binding studies and the phenylbenzoqui
none-induced writhing test. Most of these analogues exhibited a potent
analgesic activity without side effects. Among them, compound 3c (UP
202-32) bound to A(1) (K-i = 110 nM) and A(2) (K-i = 350 nM) adenosine
receptors in a specific manner since it did not interact with many ot
her receptors,especially opioid binding sites. The antinociceptive act
ivity in the phenylbenzoquinone assay (ED(50) = 3.3 mg/kg po) was anta
gonized by 8-cyclopentyl-theophylline, suggesting that an adenosinergi
c mechanism underlies the analgesic activity observed with this compou
nd. The data obtained with these new N-6-substituted adenosine recepto
r agonists emphasize the interest of such compounds in the treatment o
f pain.