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Synthesis and Biological Activity of 4‐Cycloaminopolyfluorosalicylic Acids
Author(s) -
Shchur Irina V.,
Shchegolkov Evgenii V.,
Burgart Yanina V.,
Triandafilova Galina A.,
Maslova Vera V.,
Solodnikov Sergey Yu.,
Krasnykh Olga P.,
Borisevich Sophia S.,
Khursan Sergey L.,
Saloutin Victor I.
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201803523
Subject(s) - chemistry , morpholine , pyrrolidine , amine gas treating , piperidine , nucleophilic substitution , nucleophile , alkyl , intramolecular force , hydrolysis , biological activity , adme , amino acid , catalysis , organic chemistry , stereochemistry , medicinal chemistry , biochemistry , in vitro
A series of novel 4‐cycloamino‐substituted polyfluorosalicylic acids, their esters and amides have been synthesized by the reactions of alkyl polyfluorosalicylates with morpholine, N‐methylpiperazine, pyrrolidine and proline. It was observed that esters of polyfluorosalicylic acids under prolonged heating with amines could undergo one pot nucleophilic substitution of fluorine and intramolecular acidic hydrolysis owing to catalysis by the neighboring hydroxyl group. According to ADME calculations, the synthesized compounds are suitable for drug‐design. 4‐(N‐Methylpiperazinyl)‐substituted polylfluorosalicylic acids were found to have good analgesic activity while 4‐morphonyl‐containing analogs revealed moderate anti‐inflammatory action. In addition, the presence of amine fragment in polyfluorosalicylates reduced acute toxicity comparing to non‐substituted polyfluorosalicylic acids. The molecular docking of the most active compounds was carried out into the tyrosine site of cyclooxygenase‐1.