Title : Synthesis of 2-arylhydrazinylidene-3-oxo-4,4,4-trifluorobutanoic acids as new selective carboxylesterase inhibitors and radical scavengers - Khudina_2019_Bioorg.Med.Chem.Lett__126716 |
Author(s) : Khudina OG , Makhaeva GF , Elkina NA , Boltneva NP , Serebryakova OG , Shchegolkov EV , Rudakova EV , Lushchekina SV , Burgart YV , Bachurin SO , Richardson RJ , Saloutin VI |
Ref : Bioorganic & Medicinal Chemistry Lett , :126716 , 2019 |
Abstract :
A series of 2-arylhydrazinylidene-3-oxo-4,4,4-trifluorobutanoic acids was synthesized via dealkylation of ethyl 2-arylhydrazinylidene-3-oxo-4,4,4-trifluorobutanoates under the action of a Lewis acid. Under the same conditions, ethyl 2-arylhydrazinylidene-3-oxobutanoates were also found to undergo dealkylation rather than the previously described cyclization into cinnolones. Study of the esterase profile of these compounds showed that trifluoromethyl-containing acids, in contrast to non-fluorinated analogs, were effective and selective inhibitors of carboxylesterase (CES), without substantially inhibiting structurally related cholinesterases (acetylcholinesterase and butyrylcholinesterase). Moreover, both 3-oxo-4,4,4-trifluorobutanoic and 3-oxobutanoic acids having methyl or methoxy substituent in the arylhydrazinylidene fragment showed high antioxidant activity in the ABTS test. Thus, 2-arylhydrazinylidene-3-oxo-4,4,4-trifluorobutanoic acids were found to constitute a new class of effective and selective CES inhibitors that also possess high radical-scavenging activity. |
PubMedSearch : Khudina_2019_Bioorg.Med.Chem.Lett__126716 |
PubMedID: 31640885 |
Khudina OG, Makhaeva GF, Elkina NA, Boltneva NP, Serebryakova OG, Shchegolkov EV, Rudakova EV, Lushchekina SV, Burgart YV, Bachurin SO, Richardson RJ, Saloutin VI (2019)
Synthesis of 2-arylhydrazinylidene-3-oxo-4,4,4-trifluorobutanoic acids as new selective carboxylesterase inhibitors and radical scavengers
Bioorganic & Medicinal Chemistry Lett
:126716
Khudina OG, Makhaeva GF, Elkina NA, Boltneva NP, Serebryakova OG, Shchegolkov EV, Rudakova EV, Lushchekina SV, Burgart YV, Bachurin SO, Richardson RJ, Saloutin VI (2019)
Bioorganic & Medicinal Chemistry Lett
:126716