An-Najah Staff

In this paper we report the synthesis and biological evaluation of a new class of 2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-4-ones as A3 adenosine receptor antagonists. We designed a new route based on the Kira-Vilsmeier reaction for the synthesis of this class of compounds. Some of the synthesized compounds showed A3 adenosine receptor affinity in the nanomolar range and good selectivity as evaluated in radioligand binding assays at human (h) A1, A2A, A2B, and A3 adenosine receptor subtypes. We introduced several substituents on the 2-phenyl ring. In particular substitution at the 4-position by methyl, methoxy, and chlorine gave optimal activity and selectivity 6c (KihA1, A2A>1000 nM, EC50hA2B>1000 nM, KihA3 = 9 nM), 6d (KihA1, A2A>1000 nM, EC50hA2B>1000 nM, KihA3 = 16 nM), 6b (KihA1, A2A >1000 nM, EC50hA2B>1000 nM, KihA3 = 19 nM). In conclusion, the 2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-4-one derivatives described herein represent a new family of in vitro selective antagonists for the adenosine A3 receptor.