Synthesis, anti-HCV, antioxidant, and peroxynitrite inhibitory activity of fused benzosuberone derivatives

• Published in: European journal of medicinal chemistry 2010-02, Vol.45 (2), p.492-500
• Main Authors: FARGHALY, Thoraya A, ABDEL HAFEZ, Naglaa A, RAGAB, Eman A, AWAD, Hanem M, ABDALLA, Mohamed M
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biological and medical sciences; Biphenyl Compounds - chemistry; Brain - drug effects; Brain - virology; Cricetinae; General and cellular metabolism. Vitamins; Hepacivirus - drug effects; Hepacivirus - enzymology; Heterocyclic Compounds, 2-Ring - chemical synthesis; Heterocyclic Compounds, 2-Ring - chemistry; Heterocyclic Compounds, 2-Ring - pharmacology; Medical sciences; Microbial Sensitivity Tests; Peroxynitrous Acid - antagonists & inhibitors; Pharmacology. Drug treatments; Picrates - chemistry; Pyridines - chemistry; Replicon - drug effects; Viral Nonstructural Proteins - antagonists & inhibitors
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.10.033

Reaction of benzosuberone 1 with dimethylformamide-dimethylacetal (DMF-DMA) gives 2-dimethylamino-methylenebenozosuberone 2 which in turn reacts with heterocyclic amines to furnish new heterocyclic ring systems 6-9. Moreover, enaminone 2 reacts with hydrazine hydrate and hydroxylamine hydrochloride to afford the corresponding benzo[6,7]cyclohepta[1,2-c]pyrazole (10) and benzo[6,7]cyclohepta[2,1-d]isoxazole (12), respectively. In addition, the reactions of enaminone 2 with active methylene compounds afforded benzo[6,7]cyclohepta[1,2-b]pyridines (13-18). The X-ray crystallographic analysis of compounds 6 and 16, were recorded. We demonstrated the ability of nine new synthesized compounds to inhibit Hepatitis C Virus (HCV) and Subacute Sclerosing Panencephalitis (SSPE) due to structural similarity between ribavirin and some of the newly synthesized compounds were they contain triazoles and its bioisosters. In addition, the ability of ten synthesized compounds to react with the biologically relevant reactive nitrogen species, peroxynitrite was investigated indirectly by measurement of their ability to inhibit ONOO(-)-induced tyrosine nitration. The antioxidant activity of these ten compounds was also studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay.