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A new [3 + 4] cycloaddition of azaoxyallyl cations and anthranils has been achieved for rapid access to multisubstituted benzodiazepine derivatives. A variety of anthranils and α-halo hydroxamates were both effective substrates with simple operations under transition-metal-free conditions. The intriguing features of this method include its mild nature of the reaction conditions, high efficiency, broad substrate scope, and wide functional group compatibility.N itrogen heterocycles are widespread structural motifs in bioactive natural products, therapeutic agents, agrochemicals, and material molecules with significant activities. 1 In particular, benzodiazepines, a member of the family of privileged scaffold, occupy a significant place in pharmaceutical ingredients. 2 As representative examples shown in Figure 1, SB-214857 (lotrafiban), a potent glycoprotein IIb/IIIa receptor antagonist, displays antithrombotic activity. 3 Diazepam, commercially known as Valium, is used to treat anxiety. 2a Abbemycin, isolated from Streptomyces sp. AB-999F-52, is an antibiotic. 4 TRAIL (tumor necrosis factor-related apoptosisinducing ligand)-resistance could be overcome by use of fuligocandin B. 5 Circumdatin D and E are two quinazolinobenzodiazepine alkaloids isolated from the fungus Aspergillus ochraceus. 6 Given the rich biological profiles of the sevenmembered nitrogen heterocycles in organic synthesis and medical chemistry, the development of a novel method to access benzodiazepine and related scaffolds remains highly desirable.[3 + 4]-Cycloaddition reaction is an efficient strategy to assemble seven-membered rings. 7 In recent years, azaoxyallyl

BackgroundThe impact of upregulation of platelet membrane glycoprotein (GP)IIb/IIIa and P-selectin on the onset of arterial thrombosis, venous thrombosis, and cancer encourages to hypothesize that dual inhibitor of GPIIb/IIIa and P-selectin receptors should simultaneously inhibit arterial thrombosis, block venous thrombosis, and slow tumor growth.MethodsFor this reason, the structural characteristics and the CDOCKER interaction energies of 12 carbolines were analyzed. This led to the design of 1-(4-isopropyl-phenyl)-β-carboline-3-carboxylic acid (ICCA) as a promising inhibitor of GPIIb/IIIa and P-selectin receptors.ResultsThe synthetic route provided ICCA in 48% total yield and 99.6% high-performance liquid chromatography purity. In vivo 5 μmol/kg oral ICCA downregulated GPIIb/IIIa and P-selectin expression thereby inhibited arterial thrombosis, blocked venous thrombosis, and slowed down tumor growth, but did not damage the kidney and the liver.ConclusionTherefore, ICCA could be a promising candidate capable of downregulating GPIIb/IIIa and P-selectin receptors, inhibiting arterial thrombosis, blocking venous thrombosis, and slowing down tumor growth.