Exploring the influence of the substituent at position 4 in a series of 3,4-dihydropyrimidin-2-one A.sub.2B adenosine receptor antagonists

In the context of a program to identify selective adenosine A2B receptor antagonists, we have obtained a focused library of 4-substituted 3,4-dihydropyrimidin-2(1H)-ones and its affinity for the four human adenosine receptor subtypes was determined. The synthesis was accomplished by using an experimentally simple and efficient Biginelli approach. The biological evaluation of the library revealed that all the documented derivatives exhibit low or negligible affinity for the A.sub.2B receptor, thus highlighting the critical importance of the substituent at position 4 of the 3,4-dihydropyrimidin-2(1H)-one chemotype.