title: 1,4-Benzoxazine-3(4H)-ones as potent inhibitors of platelet aggregation: design, synthesis and structure-activity relations.
abstract: A series of novel potentially platelet aggregation-inhibiting 1,4-benzoxazine-3(4H)-one derivatives was designed and synthesized through Smiles rearrangement, reduction and acetylation reactions. The antiaggregatory activities of the target molecules on arterial blood samples from rabbits, expressed by IC₅₀ values (μM), were then evaluated in vitro against ADP induced platelet aggregation. The favorable IC₅₀ values of compound 8c (IC₅₀=8.99 µM) and 8d (IC₅₀=8.94 µM) indicated that these two compounds were the most potent molecules among all the synthesized compounds. A detailed molecular docking study to explore the interaction of compounds 8c and 8d with GP IIb/IIIa receptor showed that they these two compounds were docked into the active site of GPIIb/IIIa receptor. These results suggest that the 1,4-benzoxazine-3(4H)-one derivatives are promising lead compounds to develop new platelet aggregation inhibitors.
authors.affiliation: College of Pharmaceutical Sciences, Southwest University.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Jia-Lian
authors.initials: JL
authors.lastname: Tan
authors.forename: Si-Yu
authors.initials: SY
authors.lastname: Xiao
authors.forename: Jie-Feng
authors.initials: JF
authors.lastname: Liao
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Zou
authors.forename: Xi-Xi
authors.initials: XX
authors.lastname: Ai
authors.forename: Jian-Bin
authors.initials: JB
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiang
authors.forename: Quan
authors.initials: Q
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Zuo
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D011817:Rabbits; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D048588:Benzoxazines; D010975:Platelet Aggregation Inhibitors