Synthesis and antiviral activity of some new bis-1,3-thiazole derivatives

•This manuscript reports synthesis of several novel tetra-heterocyclic derivatives.•Structures are elucidated with all possible spectral data (X-ray analysis, IR, MS, 1H and 13C NMR).•Antiviral activities against four viruses; Polio, H1N1, HBV and HCV are examined.•The SAR was studied and variously affected by the substituent's electronic factors.•One of the tested compounds showed high activity as anti HCV agent, (EC50 0.56 μM).

Treatment of 3-phenyl-1,3-thiazolidin-4-one derivative 1 with phenylisothiocyanate in DMF, in the presence of potassium hydroxide, at room temperature gave the non-isolable potassium salt 2. The in-situ reaction of 2 with differently substituted N-aryl hydrazonoyl chlorides 3, 7a–d and 14a–d afforded the corresponding 2-(pyrazolyl)thiazolylimino-5-(thiadiazolylidene)thiazolidin-4-one derivatives 6, 10a–d and 17a–d, respectively. Reaction of 2 with further α-haloketones yielded the 4-(pyrazolyl)thiazolylimino-bis-thiazolidine derivatives 22, 25 and 26. Single crystal X-ray analysis was used in structure elucidation of the products. The in-vitro antiviral screening against four viruses (Poliovirus, Influenza A (H1N1) virus, Hepatitis B virus and Hepatitis C virus) for the obtained compounds was examined. Structure activity relationship (SAR) was also studied. The goal of the work was achieved in discovering a very active compound 10a as anti HCV agent (EC50 0.56 μM).

Graphical abstractSeveral bis-1,3-thiazole derivatives incorporating pyrazole and 1,3,4-thiadiazole or 1,3-thiazole moieties have been synthesized and tested for in vitro antiviral activity against four viruses (Poliovirus, Influenza A (H1N1) virus, Hepatitis B virus and Hepatitis C virus). One of the tested compounds showed very high activity as anti HCV agent (EC50 0.56 μM).Figure optionsDownload full-size imageDownload as PowerPoint slide