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Synthesis of novel derivatives of 7,8‐dihydro‐6 H ‐imidazo[2,1‐ b ][1,3]benzothiazol‐5‐one and their virus‐inhibiting activity against influenza A virus
Author(s) -
Galochkina Anastasia V.,
Bollikanda Rakesh K.,
Zarubaev Vladimir V.,
Tentler Dmitry G.,
Lavrenteva Iri.,
Slita Alexander V.,
Chirra Nagaraju,
Kantevari Srinivas
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800225
Subject(s) - neuraminidase , virus , chemistry , zanamivir , influenza a virus , in vitro , cytotoxicity , structure–activity relationship , potency , neuraminidase inhibitor , biological activity , virology , influenzavirus b , stereochemistry , lead compound , thiophene , oseltamivir , orthomyxoviridae , biology , biochemistry , medicine , covid-19 , organic chemistry , disease , pathology , infectious disease (medical specialty)
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‐6 H ‐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.