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.

Autor: Galochkina AV; Pasteur Institute of Epidemiology and Microbiology, St. Petersburg, Russia., Bollikanda RK; Fluoro and Agrochemicals Division (Organic Chemistry Division-II), CSIR - Indian Institute of Chemical Technology, Hyderabad, India.; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Chemical Technology, Hyderabad, India., Zarubaev VV; Pasteur Institute of Epidemiology and Microbiology, St. Petersburg, Russia., Tentler DG; Institute of Cytology, Russian Academy of Sciences, Russia., Lavrenteva IN; Pasteur Institute of Epidemiology and Microbiology, St. Petersburg, Russia., Slita AV; Pasteur Institute of Epidemiology and Microbiology, St. Petersburg, Russia., Chirra N; Fluoro and Agrochemicals Division (Organic Chemistry Division-II), CSIR - Indian Institute of Chemical Technology, Hyderabad, India.; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Chemical Technology, Hyderabad, India., Kantevari S; Fluoro and Agrochemicals Division (Organic Chemistry Division-II), CSIR - Indian Institute of Chemical Technology, Hyderabad, India.; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Chemical Technology, Hyderabad, India.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2019 Feb; Vol. 352 (2), pp. e1800225. Date of Electronic Publication: 2018 Dec 06.
DOI: 10.1002/ardp.201800225
Abstrakt: 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.
(© 2018 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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