Synthesis and Biological Activity of 4‐Cycloaminopolyfluorosalicylic Acids. Issue 4 (29th January 2019)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: ChemistrySelect. Volume 4:Issue 4(2019)
• Page Start: 1483
• Page End: 1490
• Publication Date: 2019-01-29
• Subjects: amidation -- biological activity -- intramolecular hydrolysis -- nucleophilic substitution -- polyfluorosalicylates; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201803523
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: 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. Abstract : Esters of polyfluorosalicylic acids under prolonged heating with cyclic amines (morpholine, N‐methylpiperazine, pyrrolidine and proline) have undergone one pot nucleophilic substitution of fluorine and intramolecular acidic hydrolysis owing to catalysis by the neighboring hydroxyl group. 4‐(N‐Methylpiperazinyl)‐substituted polylfluorosalicylic acids have good analgesic activity while 4‐morphonyl‐containing analogs revealed moderate anti‐inflammatory action. The introduction of amine fragment in polyfluorosalicylates decreases acute toxicity comparing to non‐substituted polyfluorosalicylic acids.