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RAS Chemistry & Material ScienceЖурнал органической химии Russian Journal of Organic Chemistry

  • ISSN (Print) 0514-7492
  • ISSN (Online) 3034-6304

Features of Conjugation of Ipidacrine Chloroalkylamides with 5-Acetyl-3-(Trifluoromethyl)Pyrazole and Its Derivatives. Study of Biological Activity

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PII
S3034630425070131-1
DOI
10.7868/S3034630425070131
Publication type
Article
Status
Published
Authors
O. G. Khudina
  • Affiliation: I.Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences
D. N. Bazhin
  • Affiliation:
    I.Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences
    Ural Federal University named after the first President of Russia B.N. Yeltsin
G. F. Makhaeva
  • Affiliation: Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences
Y. V. Burgart
  • Affiliation: I.Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences
N. V. Kovaleva
  • Affiliation: Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences
N. P. Boltneva
  • Affiliation: Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences
E. V. Rudakova
  • Affiliation: Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences
T. S. Skornjakova
  • Affiliation: Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences
V. I. Saloutin
  • Affiliation: I.Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences
Volume/ Edition
Volume 61 / Issue number 7
Pages
917-933
Abstract
An approach to the preparation of ipidacrine conjugates with trifluoromethyl pyrazoles containing acetyl, hydrazone or oxime groups as functional substituents has been investigated. The alkylation of 5-acetyl-3-(trifluoromethyl)pyrazole with 2-chloroacetamide of ipidacrine proceeds non-regioselectively on the nitrogen atoms of the pyrazole ring, giving a mixture of 3-/5-CF-regioisomeric products. The introduction of a hydrazone/oxime substituent into the structure of CF-pyrazoles leads to the preferential formation of 3-CF-regioisomeric conjugates. In alkylation reactions, preservation of the arylhydrazone substituent in pyrazolyl-containing ipidacrines is observed, whereas the oxime group undergoes hydrolysis to the acetyl function. Conjugation of 5-(1-hydroxizimylidenethyl)pyrazole with 3-chloropropanamide of ipidacrine was accompanied by partial reduction of the hydrazone substituent. 4-Chlorobutanamide of ipidacrine in MeCN did not react with pyrazoles, and upon heating in DMF 5-(1-hydroxizimylidenethyl)pyrazole underwent transamination to form symmetric ketazine. The conjugate with the N-propanamide spacer showed moderate selective inhibitory activity towards butyrylcholinesterase (IC = 14.5 ± 0.8 μM) and towards self-aggregation of β-amyloid (1–42). The introduction of an aryl substituent into the hydrazone fragment led to an increase in the antioxidant activity of pyrazoles and to the appearance of significant antioxidant properties of the conjugates in the ABTS (TEAC = 0.47–0.56) and FRAP (0.44–0.55 TE) tests.
Keywords
ипидакрин трифторметилпиразол конъюгаты алкилирование ингибиторы антихолинэстеразная антиоксидантная и антиагрегантная активность
Date of publication
01.07.2025
Year of publication
2025
Number of purchasers
0
Views
25

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