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Synthesis and anti‐coronavirus activity of a series of 1‐thia‐4‐azaspiro[4.5]decan‐3‐one derivatives
Author(s) -
Apaydın Çağla Begüm,
Cesur Nesrin,
Stevaert Annelies,
Naesens Lieve,
Cesur Zafer
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.201800330
Subject(s) - amide , benzamide , chemistry , stereochemistry , ec50 , coronavirus , virus , lead compound , influenza a virus , chemical synthesis , virology , structure–activity relationship , in vitro , covid-19 , biology , biochemistry , medicine , disease , pathology , infectious disease (medical specialty)
Abstract A series of 1‐thia‐4‐azaspiro[4.5]decan‐3‐ones bearing an amide group at C‐4 and various substitutions at C‐2 and C‐8 were synthesized and evaluated against human coronavirus and influenza virus. Compounds 7m , 7n , 8k , 8l , 8m , 8n , and 8p were found to inhibit human coronavirus 229E replication. The most active compound was N ‐(2‐methyl‐8‐ tert‐ butyl‐3‐oxo‐1‐thia‐4‐azaspiro[4.5]decan‐4‐yl)‐3‐phenylpropanamide ( 8n ), with an EC 50 value of 5.5 µM, comparable to the known coronavirus inhibitor, ( Z )‐ N ‐[3‐[4‐(4‐bromophenyl)‐4‐hydroxypiperidin‐1‐yl]‐3‐oxo‐1‐phenylprop‐1‐en‐2‐yl]benzamide ( K22 ). Compound 8n and structural analogs were devoid of anti‐influenza virus activity, although their scaffold is shared with a previously discovered class of H3 hemagglutinin‐specific influenza virus fusion inhibitors. These findings point to the 1‐thia‐4‐azaspiro[4.5]decan‐3‐one scaffold as a versatile chemical structure with high relevance for antiviral drug development.