1450892-97-3Relevant academic research and scientific papers
Discovery of the 2-phenyl-4,5,6,7-Tetrahydro-1 H -indole as a novel anti-hepatitis C virus targeting scaffold
Andreev, Ivan A.,Manvar, Dinesh,Barreca, Maria Letizia,Belov, Dmitry S.,Basu, Amartya,Sweeney, Noreena L.,Ratmanova, Nina K.,Lukyanenko, Evgeny R.,Manfroni, Giuseppe,Cecchetti, Violetta,Frick, David N.,Altieri, Andrea,Kaushik-Basu, Neerja,Kurkin, Alexander V.
, p. 250 - 258 (2015)
Although all-oral direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) treatment is now a reality, today's HCV drugs are expensive, and more affordable drugs are still urgently needed. In this work, we report the identification of the 2-phenyl-4,5,6,7-Tetrahydro-1H-indole chemical scaffold that inhibits cellular replication of HCV genotype 1b and 2a subgenomic replicons. The anti-HCV genotype 1b and 2a profiling and effects on cell viability of a selected representative set of derivatives as well as their chemical synthesis are described herein. The most potent compound 39 displayed EC50 values of 7.9 and 2.6 μM in genotype 1b and 2a, respectively. Biochemical assays showed that derivative 39 had no effect on HCV NS5B polymerase, NS3 helicase, IRES mediated translation and selected host factors. Thus, future work will involve both the chemical optimization and target identification of 2-phenyl-4,5,6,7-Tetrahydro-1H-indoles as new anti-HCV agents.
Synthesis of 4,5,6,7-tetrahydro-1H-indole derivatives through successive sonogashira coupling/Pd-mediated 5-endo-dig cyclization
Andreev, Ivan A.,Belov, Dmitry S.,Kurkin, Alexander V.,Yurovskaya, Marina A.
, p. 649 - 652 (2013/03/13)
A one-pot Sonogashira cross-coupling/5-endo-dig cyclization procedure leading to 2-aryl-4,5,6,7-tetrahydroindoles was developed. This short (only two steps from commercially available compounds) sequence avoids harsh conditions and expensive catalysts. Our procedure is highly tolerant to a range of functional groups (amino, nitro, carboxy, cyano, hydroxy, and bromo). A family of 21 tetrahydroindoles was synthesized on a gram scale in a good to excellent yields, which is indicative of the general character and scalability of this reaction. This methodology allows access to indoles bearing miscellaneous substituents at the C2 position (by variation of ArI) and at the nitrogen atom (by variation of RNH2, including chiral moieties). A one-pot sequence based on Sonogashira cross-coupling/Pd-mediated 5-endo-dig cyclization was developed and applied to the gram-scale synthesis of 2-aryl-4,5,6,7- tetrahydroindoles (21 examples). Copyright
