NOVEL UBSTITUTED-PHENYLCARBAMOYL)ADENOSINE-5'-URONAMIDES AS POTENT AGONISTS FOR A(3) ADENOSINE RECEPTORS

A series of adenosine-5'-uronamide derivatives bearing N-6-phenylurea groups have been synthesized and tested for their affinity at A(1) and A(2A) adenosine receptors in rat brain membranes and at cloned rat A( 3) receptors from stably transfected CHO cells. Some N-6-arylcarbamoyl derivatives, N-6-((2-chlorophenyl)carbamoyl)-, N-6-((3-chlorophenyl)c arbarmoyl)-, and ethoxyphenyl)carbamoyl)adenosine-5'-ethyluronamide (4 1-n), were found to have affinity at A(3) receptors in the low nanomol ar range (K-i values < 10 nM). In CHO cells stably transfected with th e rat A(3) receptor, compound 4n was found to be a full agonist in inh ibiting adenylate cyclase activity. The present study represents the f irst example of N-6-acyl-substituted adenosine analogs having high aff inity at adenosine receptors and, in particular, at the A(3) receptor subtype.