N.V. Kolotova Ph.D. (Chem.), Associate Professor, Perm State Pharmaceutical Academy (Perm) E-mail: S.V. Chashchina Ph.D. (Biol.), Associate Professor, Perm State Pharmaceutical Academy (Perm)

The search for new compounds with anti-inflammatory and analgesic effects is relevant. The goal - the search for compounds with anti-inflammatory and analgesic activities among monosubstituted amides and hydrazides of 1, 4-dicarboxylic acids. Material and methods. Objects of study - acylamides and acylhydrazides of 1, 4-dicarboxylic acids. A study of anti-inflammatory activity was car-ried out for 11 compounds on white non-linear rats of both sexes weighing 190-220 g (6 animals) in a model of acute inflammatory edema (administra-tion of 0.1 ml of a 1% aqueous solution of carrageenin). An increase in foot volume was evaluated oncometrically before administration and 3 hours af-ter administration of carrageenin. The test substances were administered orally at a dose of 50 mg / kg 1 hour before the administration of the phlogo-genic agent. Standard: the drug «Nimesulide-MBF» Control: animals not receiving the drug. The presence of anti-inflammatory action was judged by the severity of inhibition of the inflammatory reaction. Analgesic activity was determined for 9 compounds on white non-linear mice weighing 25-30 g (8 animals) according to the method of «hot plate». Compounds were administered intraperitoneally 30 minutes before testing at a dose of 50 mg / kg. Standard: the drug «Metamizole Sodium» The animals were placed on a metal surface heated to 56 ° C. The time was recorded from the moment it was placed on a hot surface until a behavioral response to pain irritation appeared. A criterion for the analgesic effect was considered a significant in-crease in the latent period of the reaction after administration of the substance. The animals of the control group were injected with an equivolume amount of physiological sodium chloride solution. Results. It was found that maleic acid 2-pyrimidylamide, 4-methyl-2-pyridylamide and citraconic acid 2-thiazolylamide showed pronounced anti-inflammatory activity. High analgesic activity was found for 3-hydroxy-4-carboxyphenylamide maleic acid and 4-methoxybenzoylhydrazide phthalic ac-id. 4-Methyl-2-pyridylamide of citraconic acid exceeds the effect of the drug «Metamizole sodium» and has an anti-inflammatory effect at the level of the drug «Nimesulide». Findings. It is recommended to continue the search among the derivatives of 1,4-dicarboxylic acids for compounds with anti-inflammatory and anal-gesic effects.

derivatives of 1
4-dicarboxylic acids
anti-inflammatory activity

  1. Nasonov A.E., Karataev A.A. Nesteroidnye protivovospalitel'nye preparaty: klinicheskie rekomendacii po ispol'zovaniju. Vrach. 2007; 3: 8–14.
  2. Burdulene D., Palajma A., Stumbrjavichjute Z., Talajkite Z. Sintez i protivovospalitel'naja aktivnost' sukcinamidov, proizvodnyh 4-aminoantipirina. Himiko-farmacevticheskij zhurnal. 1999; 4: 20–22.
  3. Burdulene D., Palajma A., Stumbrjavichjute Z. i dr. Sintez i anal'geticheskaja aktivnost' nekotoryh N,N'-zameshhennyh sukcindiamidov. Himiko-farmacevticheskij zhurnal. 1999; 5:35–36.
  4. Burduliene D., Palaima A., Stumbreviciute Z. et al. Antiinflammatory action of succinic acid diamides substituted with amino acid residues. Biologija. 1998; 4:27–31.
  5. Koz'minyh V.O., Kolla V.Je., Shelenkova S.A. i dr. Zameshhjonnye amidy i gidrazidy maleinovoj kisloty. II. Sintez i biologicheskaja aktivnost' ariliden- i diarilmetilengidrazidov maleinovoj kisloty. Himiko-farmacevticheskij zhurnal. 1993; 1: 45–51.
  6. Kolotova N.V., Koz'minyh E.N., Kolla V.Je. i dr. Zameshhjonnye amidy i gidrazidy 1,4-dikarbonovyh kislot. 7. Sintez i biologicheskaja aktivnost' nekotoryh acilgidrazidov maleinovoj, jantarnoj i ftalevoj kislot. Himiko-farmacevticheskij zhurnal. 1999; 5: 22–28.
  7. Dolzhenko A.V. Sintez, struktura i biologicheskaja aktivnost' soedinenij, poluchennyh na osnove reakcij vzaimodejstvija ciklicheskih angidridov dikarbonovyh kislot s nukleofil'nymi reagentami: Diss. .... kand. farm. nauk. Perm'. 2003. S. 173.
  8. Kolotova N.V., Chashhina S.V. Anal'geticheskaja aktivnost' monozameshhennyh amidov i gidrazidov 1, 4-dikarbonovyh kislot. Voprosy obespechenija kachestva lekarstvennyh sredstv. 2019; 2: 34–39.
  9. Mironov A.N. (red.) Rukovodstvo po provedeniju doklinicheskih issledovanij lekarstvennyh sredstv. M.: Grif i K, 2012; s. 944.
  10. Prozorovskij V.V. Statisticheskaja obrabotka rezul'tatov farmakologicheskih issledovanij. Psihofarmakologija i biologicheskaja narkologija. 2007; 7.
  11. Vyp. 3-4: 2090–2120.