2020 / 01

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DOI: 10.24075/brsmu.2020.007

ORIGINAL RESEARCH

Synthesis of a novel amide derivative of valproic acid and 1,3,4-thiadiazole with antiepileptic activity

Malygin AS1, Demidova MA1, Skachilova SYa2, Shilova EV2
About authors

1 Tver State Medical University, Tver, Russia

2 All-Russian Research Center for the Safety of Bioactive Substances, Staraya Kupavna, Moscow region, Russia

Correspondence should be addressed: Alexandr S. Malygin
Sovetskaya, 4, Tver, 170100; ur.xednay@m.s.a.rd

About paper

Compliance with ethical standards: the study was approved by the Ethics Committee of Tver State Medical University (Protocol № 4 dated March 26, 2018). The animals were treated in compliance with the guidelines for laboratory practice in preclinical trials (Order 199n of the Russian Ministry of Healthcare dated April 1, 2016, on the Good laboratory practice). All tests were carried out in accordance with the guidelines for preclinical trials of medicinal drugs and in compliance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and other Scientific Purposes (Directive 2010/63/EU).

Author contribution: Malygin AS — laboratory tests; data analysis; literature analysis; manuscript preparation; Demidova MA — study concept and design; manuscript preparation; Skachilova SYa, Shilova EV— synthesis and analysis of the compound; All authors equally contributed to the discussion of the study results.

Received: 2020-01-17 Accepted: 2020-02-03 Published online: 2020-02-10
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Fig. 1. N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propyl pentane amide
Fig. 2. A schematic representation of N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propyl pentane amide synthesis. 1 — 2-propylpentanoic acid; 2 — thionyl chloride; 3 — 2-propylpentanoic acid chloroanhydride; 4 — 2-amino-5-ethyl-1,3,4-thiadiazole; 5 — N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2- propyl pentane amide
Fig. 3. ESI+-mass-spectrum of N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propyl pentane amide ([M + H]+)
Fig. 4. A chromatogram of N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propyl pentane amide
Table. The effect of N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propyl pentane amide (VPZ) on the latency to the first seizure and survival of mice in the test with the VPZ antagonist isoniazid (250 mg/kg injected intraperitoneally)
Note: * — statistically significant difference between the experimental group and the control animals (mice with isoniazid-induced seizures treated with NaCl IS before the isoniazid injection) (р < 0.05; one-way ANOVA with post-hoc Tukey HSD); # — statistically significant difference between the experimental group and the control (р < 0.05; Fisher’s exact test). VPZ is valprazolamide (N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propyl pentane amide); INH is isoniazid; NaCl IS is the isotonic solution of sodium chloride; LS1 is latency to the first seizure.