Novel nitric oxide-releasing isochroman-4-one derivatives: Synthesis and evaluation of antihypertensive activity.
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.
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, PR China.
Renren
R
Bai
Xue
X
Yang
Yao
Y
Zhu
Zhiwen
Z
Zhou
Weijia
W
Xie
Hequan
H
Yao
Jieyun
J
Jiang
Jie
J
Liu
Mingqin
M
Shen
Xiaoming
X
Wu
Jinyi
J
Xu
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D002867:Chromones; D020030:Nitric Oxide Donors; D009569:Nitric Oxide