1,4-Benzoxazine-3(4<i>H</i>)-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 IC 50 values (μM), were then evaluated in vitro against ADP induced platelet aggregation. The favorable IC 50 values of compound 8c (IC 50 8.99 µM) and 8d (IC 50 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.

9,10-Phenanthrenedione as Visible-Light Photoredox Catalyst: A Green Methodology for the Functionalization of 3,4-Dihydro-1,4-Benzoxazin-2-Ones through a Friedel-Crafts Reaction

“…Hence, exploring other substrates is highly desirable. In this context, 1,4-dibenzoxazinone skeleton is present in a wide number of compounds with biological activities and its functionalization could be significant and interesting for medicinal chemistry [63][64][65][66][67][68][69]. Very recently, Huo described the iron catalyzed sp 3 -C-H functionalization of 3,4-dihydro-1,4-benzoxazin-2-ones [70,71] using as a terminal oxidant tert-Butyl hydroperoxide (TBHP) [70] or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) [71].…”

9,10-Phenanthrenedione as Visible-Light Photoredox Catalyst: A Green Methodology for the Functionalization of 3,4-Dihydro-1,4-Benzoxazin-2-ones through a Friedel-Crafts Reaction

“…In this context, 1,4-dibenzoxazinone skeleton is present in a wide number of compounds with biological activities and its functionalization could be significant and interesting for medicinal chemistry. [64][65][66][67][68][69][70] Very recently, Huo described the iron catalyzed sp 3 -C-H functionalization of 3,4-dihydro-1,4-benzoxazin-2-ones [71][72] using as a terminal oxidant TBHP [71] or DDQ [72]. We envisioned that this functionalization could be achieved by a visible-light photochemical process.…”

Progress of thrombus formation and research on the structure-activity relationship for antithrombotic drugs

“…Chemical structures of ferulic acid derivatives 90-92.Exposure of GPIIb/IIIa receptors on the surface of platelets can promote the binding of fibrinogen molecules to platelets, causing the aggregate of platelets and leading to thrombosis. Liu et al[105] synthesized a series of compounds with inhibitory activity of GPIIb/IIIa receptor by different chemical substitutions at 7-position and 4-position of 1,4-benzoxazine-3(4H)-one (Fig.63). In the anti-platelet aggregation activity test of rabbit arterial blood samples, using aspirin and ticlopidine…”