A new series of 5-substituted and 5-nonsubstituted pyrazolopyrrolopyrimidine derivatives were synthesized, and their vasorelaxing and hypotensive activities were evaluated. The syntheses were efficiently accomplished through the use of three key intermediates (7, 16, and 24), as shown in Schemes I-III. The desired pharmacological activities were confirmed on the basis of vasorelaxing activity in rat aorta (in vitro) and hypotensive activity in rats (in vivo). Specifically, compound 25 exhibited the strongest activity and appears to be a promising clinical lead for the development of a new antihypertensive agent.