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).

Several 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 as PowerPoint slide