Scholarlink

Abstract <p>An approach to the preparation of ipidacrine conjugates with trifluoromethyl pyrazoles containing acetyl, hydrazone, or oxime groups as functional substituents has been studied. 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<sub>3</sub>-regioisomeric products. The introduction of a hydrazone/oxime substituent into the structure of CF<sub>3</sub>-pyrazoles leads to the preferential formation of 3-CF<sub>3</sub>-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-hydrazinylidenethyl)pyrazole with 3-chloropropanamide of ipidacrine is 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-hydrazinylideneethyl)pyrazole underwent transamination to form a symmetric ketazine. The conjugate with the <i>N</i>-propanamide spacer showed moderate selective inhibitory activity towards butyrylcholinesterase (IC<sub>50</sub> = 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2025年6月1日

查看全文
  • O. G. Khudina,
  • D. N. Bazhin,
  • G. F. Makhaeva,
  • Y. V. Burgart,
  • N. V. Kovaleva,
  • N. P. Boltneva,
  • E. V. Rudakova,
  • T. S. Skornyakova,
  • V. I. Saloutin

摘要

Abstract

An approach to the preparation of ipidacrine conjugates with trifluoromethyl pyrazoles containing acetyl, hydrazone, or oxime groups as functional substituents has been studied. 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-CF3-regioisomeric products. The introduction of a hydrazone/oxime substituent into the structure of CF3-pyrazoles leads to the preferential formation of 3-CF3-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-hydrazinylidenethyl)pyrazole with 3-chloropropanamide of ipidacrine is 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-hydrazinylideneethyl)pyrazole underwent transamination to form a symmetric ketazine. The conjugate with the N-propanamide spacer showed moderate selective inhibitory activity towards butyrylcholinesterase (IC50 = 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.