Influence of 6 or 8-substitution on the antiviral activity of 3-phenethylthiomethylimidazo[1,2-a]pyridine against human cytomegalovirus (HCMV) and varicella-zoster virus (VZV)

Abstract

The synthesis of original imidazo[1,2-a]pyridines bearing a phenethylthiomethyl side chain at the 3 position and a (hetero)aryl substituent on the 6 or 8 position, and their antiviral activities are reported. From the synthesized compounds, the 6-halogeno and 6-phenylimidazo[1,2-a]pyridine derivatives 4c-d and 5b were the most potent against human cytomegalovirus (CMV) and/or varicella-zoster virus (VZV), whereas several other congeners (i.e., 5e, 5g, 5i, 5l, 5n, 5p, 5q, and 5t), while less potent, were equally or more selective in their inhibitory activity against both VZV and CMV. These compounds showed similar activity against thymidine kinase competent (TK(+)) and deficient (TK(-)) VZV strains, demonstrating a mechanism of action independent of the viral thymidine kinase.

One-Pot Synthesis of 2-Phenylimidazo[1,2-α]pyridines from Acetophenone, [Bmim]Br3 and 2-Aminopyridine under Solvent-Free Conditions

“…Imidazo[1,2-α]pyridines are of interest because of the occurrence of their saturated and partially saturated derivatives in a variety of biologically active compounds, which have been shown to possess a broad range of useful pharmacological properties [ 1 ], including anti-inflammatory [ 2 , 3 ], antiprotozoal [ 4 ], antiviral [ 5 , 6 , 7 ], antiulcer [ 8 , 9 ], antibacterial [ 10 , 11 ], antifungal [ 12 ], antiprotozoal [ 4 , 13 ], antiherpes [ 14 , 15 ] and treatment of hepatitis C [ 16 ], and HIV [ 17 ], etc. They are also versatile intermediates for synthetic transformations [ 18 , 19 ].…”

Structural characterization and Hirshfeld surface analysis of a CoII complex with imidazo[1,2-a]pyridine

“…In the realm of the synthesis of heterocyclic compounds, imidazopyridines have proven to be a most important class of molecules and have attracted significant interest because of their promising applications. They are biologically important and have shown a wide variety of pharmacological effects (Adib et al, 2011): anti-inflammatory (Rupert et al, 2003), antiviral (Puerstinger et al, 2007), antiulcer (Kaminski & Doweyko, 1997), antibacterial (Rival et al, 1992), antifungal (Rival et al, 1991), antiprotozoal (Biftu et al, 2006;Ismail et al 2008), antiherpes (Gudmundsson & Johns, 2007;Vé ron et al, 2007), and for the treatment of hepatitis C (Bravi et al, 2007), and HIV (Gudmundsson & Boggs, 2007). These medically relevant compounds exhibit a wide range of activities including anti-herpes, antiapoptotic, sedative, anxiolytic, anticonvulsant, muscle relaxant, analgesic, antituberculosis and anticancer actions (Dymiń ska, 2015;Bagdi et al, 2015).…”

Ultrasound-Assisted Iodination of Imidazo[1,2-α]pyridines Via C–H Functionalization Mediated by tert-Butyl Hydroperoxide

“…In the past 20 years, with the development of the chemical and pharmaceutical industries, novel approaches to the synthesis of heterocycles have rapidly emerged. − The development of more green and effective methods to heterocycle synthesis has been a major research interest for green and sustainable chemists because more than 70% of major commercially available synthetic drugs contain at least one N -fused heterocyclic scaffold. − It is worth mentioning that the imidazo­[1,2-α]­pyridine derivatives exhibit a wide range of biological and pharmacological activities, such as antibacterial, antiulcer, antiviral, and antitumor (Scheme ). − As a result, tremendous efforts have been devoted to the synthesis and functionalization of N -fused heterocyclic scaffolds. − Among them, 3-halo imidazo­[1,2-α]­pyridines are great potential intermediates for their diverse reactivity in many types of reactions.…”

“…Hz, 1 H), 8.03 (d, J = 4.8 Hz, 2 H), 7.81 (s, 1 H), 7.48 (t, J = 5.0 Hz, 2 H), 7.41 (t, J = 4 8. Hz, 1 H),7.02 (dd, J = 4.8, 0.8 Hz, 1 H);13 C NMR (101 MHz, CDCl 3 ) δ 148.96, 148.11, 133.18, 128.75, 128.61, 128.56, 126.88, 119.79, 119.52, 117.18, 59.99; HRMS (ESI-TOF) m/z calcd for C 13 H 9 BrIN 2 [M + H] + : 398.8988, found: 398.8993. CDCl 3 ) δ 8.09 (d, J = 7.2 Hz, 2 H), 7.86 (d, J = 6.8 Hz, 1 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.36 (t, J = 7.2 Hz, 1 H), 6.81 (t, J = 7.6 Hz, 1 H), 6.55 (d, J = 7.4 Hz, 1 H), 4.02 (s, 3 H); 13 C NMR (101 MHz, CDCl 3 ) δ 148.90, 147.29, 142.43, 133.50, 128.76, 128.29, 128.24, 119.53, 112.90, 101.72, 60.51, 56.17; MS: m/z 350 (M + ).…”