title: Design, synthesis and evaluation of nitric oxide releasing derivatives of 3-n-butylphthalide as antiplatelet and antithrombotic agents.
abstract: Novel nitric oxide (NO) releasing derivatives (7a-7l) of 3-n-butylphthalide (NBP) were designed and synthesized. Compound 7e inhibited the adenosine diphosphate (ADP), thrombin (TH) and arachidonic acid (AA)-induced in vitro platelet aggregation, superior to NBP and aspirin, released moderate levels of NO, and improved aqueous solubility relative to NBP. Furthermore, 7e exhibited greater antithrombotic activity than NBP and aspirin in rats, and protected against collagen and adrenaline-induced thrombosis in mice. Therefore, NO-releasing NBP derivatives possessed potent antiplatelet aggregation and antithrombotic activity. Our findings may aid in the design of new therapeutic agents for the treatment of thrombosis-related ischemic stroke.
authors.affiliation: Center of Drug Discovery, China Pharmaceutical University, Nanjing, P R China.
authors.forename: Xuliang
authors.initials: X
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Min
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Lai
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.forename: Sixun
authors.initials: S
authors.lastname: Peng
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D004357:Drug Synergism; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000188:drug therapy
chemical_list: D001572:Benzofurans; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; C027125:3-n-butylphthalide