Novel nitric oxide-releasing isochroman-4-one derivatives: Synthesis and evaluation of antihypertensive activity.

Abstract By coupling nitric oxide (NO)-donor moieties with a natural antihypertensive product (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] and its analogue (±)-XJP-B, a series of novel NO-releasing isochroman-4-one derivatives were designed and synthesized. The NO-releasing assay indicated that compounds Ia , Id , IIIb and IIIe released the maximum amount of NO. The maximum reductions of blood pressure of Ia , IIIb and IIIe in SHRs were nearly 40%, which was obviously superior to that of the lead compounds and comparable to that of reference drug captopril. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel antihypertensive agents.