Synthesis of novel derivatives of 7,8‐dihydro‐6H‐imidazo[2,1‐b][1,3]benzothiazol‐5‐one and their virus‐inhibiting activity against influenza A virus

Abstract

Influenza remains a highly pathogenic and hardly controlled human infection. The ability of selecting drug-resistant variants necessitates the search and development of novel anti-influenza drugs. Herein, we describe the synthesis and evaluation of a series of novel 2-substituted 7,8-dihydro-6H-imidazo[2,1-b][1,3]benzothiazol-5-ones 3a-k for their virus-inhibiting activity against influenza A virus. The new analogues 3a-k prepared in two steps from commercially available cyclohexane-1,3-diones were fully characterized by their NMR and mass spectral data. Among the new derivatives screened for cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells, three analogues 3i-k containing a thiophene unit were found to exhibit high virus-inhibiting activity (high SI values) and a favorable toxicity profile. The compound 3j (CC 50 : >1000 μM, SI = 77) with higher potency is the best anti-influenza hit analogue for further structural optimization and drug development. The most active compounds did not inhibit viral neuraminidase and possess therefore other targets and mechanisms of activity than the currently used neuraminidase inhibitors.

Thiazole Ring—A Biologically Active Scaffold

“…Galochkina et al [147] described the synthesis and biological evaluation of a series of novel imidazo[2,1-b] thiazole-based compounds (96a-k) as potential inhibitors of influenza virus in vitro (Figure 37). Compounds were tested against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells [145].…”

Benzothiazoles as potential antiviral agents

“…To get insight into the molecular mechanism of its anti-influenza potential, a detailed NA enzyme inhibition assay was also carried out; however, the result was not significant (Figure 20). [96] Bcl-2 inhibitors…”

Synthesis of new heterocycles festooned with thiophene and evaluating their antioxidant activity

“…Substituted 7,8-dihydro-imidazo [2,1-b]benzothiazol-5-one derivatives were screened for their virus-inhibiting activity against influenza A virus. [29] Depending on the significant pharmacological interests mainly antioxidant activity of substituted thiophenes, there is a strong inspiration for the continuous synthesis of new heterocyclic systems incorporating substituted thiophene moiety. Therefore, further continuation of our previous work, [30][31][32][33][34] we are informing here the synthesis of some more analogs of various heterocyclic systems (namely; imidazo-thiazole, imidazo-tetrazole, imidazotriazole, imidazo-pyridine, imidazo-imidazole, thiazole and/or thiophene) incorporating 2-thienyl moiety and evaluating their in vitro anti-oxidant activity.…”

“…Substituted 7,8‐dihydro‐imidazo[2,1‐ b ]benzothiazol‐5‐one derivatives were screened for their virus‐inhibiting activity against influenza A virus. [ 29 ]…”