SYNTHESIS AND PRIMARY SCREENING OF ANTI-INFLAMMATORY ACTIVITY OF 1,4,5,6-TETRAHYDROPYRIMIDINE-2-CARBOXAMIDES

Authors

  • V. Ya. Horishny Danylo Halytsky Lviv National Medical University
  • D. A. Frolov Ivan Franko National University of Lviv
  • I. O. Nektegayev Ivan Franko National University of Lviv
  • Yu. V. Ostapiuk Ivan Franko National University of Lviv
  • V. S. Matiychuk Ivan Franko National University of Lviv

DOI:

https://doi.org/10.11603/2312-0967.2018.2.9125

Keywords:

organic synthesis, pyrimidine, thioxoacetamide, thiazole, morpholine, anti-inflammatory activity.

Abstract

The aim of the work. Development of methods for obtaining new morpholin-4-yl-2-thioxoacetamides and investigate their reaction with 1,3-diaminopropane; synthesis of new 1,4,5,6-tetrahydropyrimidine-2-carboxamides and primary screening of their anti-inflammatory properties.

Materials and Methods. Organic synthesis, NMR spectroscopy, elemental analysis, pharmacological screening.

Results and Discussion. By the reaction of chloroacetamides with sulfur and morpholine a series of 2-morpholin-4-yl-2-thioxoacetamides were synthesized. They were investigated in the reaction with 1,3-diaminopropane. As a result, the series of new 1,4,5,6-tetrahydropyrimidine-2-carboxamides were prepared. The anti-inflammatory activity of some synthesized compounds has been investigated.

Conclusions. The method of synthesis of 1,4,5,6-tetrahydropyrimidine-2-carboxamides was developed. The results of anti-inflammatory activity investigation of synthesized compounds allowed us to identify highly active derivatives which was appropriate to the reference non-steroidal antiinflammatory drug “Diclofenac Sodium” by indicator of inhibition of inflammatory reaction (37.5–46.7 %).

Author Biographies

V. Ya. Horishny, Danylo Halytsky Lviv National Medical University

docent of the department of   pharmaceutical, organic and bioorganic chemistry, Danylo Halytsky Lviv National Medical University

D. A. Frolov, Ivan Franko National University of Lviv

aspirant of the department of organic chemistry, Ivan Franko National University of Lviv

I. O. Nektegayev, Ivan Franko National University of Lviv

docent of the department of organic chemistry, Ivan Franko National University of Lviv

Yu. V. Ostapiuk, Ivan Franko National University of Lviv

docent of the department of organic chemistry, Ivan Franko National University of Lviv

V. S. Matiychuk, Ivan Franko National University of Lviv

profesor of the department of organic chemistry, Ivan Franko National University of Lviv

References

Van Vranken DL, Weiss GA. Introduction to bioorganic chemistry and chemical biology. Garland Science; 2013. 486p.

Mashkovsky МD. Medicinal products. [Лекарственные средства]. Мoscow: New Wave; 2010. Russian.

Kikkeri N Mohanaa, Basavapatna N Prasanna Kumara, Lingappa Malleshab. Synthesis and biological activity of some pyrimidine derivatives. Drug Invention Today. 2013;5(3):216-22.

Alam MdJ, Alam O, Shrivastava N, Naim MdJ, Alam P. Pyrimidine candidate as promising scaffold and their biological evaluation. International Journal of Pharmacology and Pharmaceutical Sciences. 2015;2(4):55-69.

Asif M. Mini review on synthetic methods and biological activities of various substituted Pyrimidine derivatives. Moroccan Journal of Chemistry. 2016;4:961-75.

Abida PN, Arpanarana M. An updated review: Newer quinazoline derivatives under clinical trial. Int J Pharmaceut Biol Arch. 2011;2:1651-7.

Nara H, Sato K, Naito T, Mototani H, Oki H, Yamamoto Y, et al. Discovery of novel, highly potent, and selective quinazoline-2-carboxamide-based matrix metalloproteinase (MMP)-13 inhibitors without a zinc binding group using a structure-based design approach. Journal of Medicinal Chemistry. 2014;57(21):8886-902.

Nara H, Sato K, Naito T, Mototani H, Oki H, Yamamoto Y, et al. Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: Highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1'' binding site. Bioorganic & Medicinal Chemistry. 2014;22(19):5487-505.

Sielecki TM, Johnson TL, Liu J, Muckelbauer JK, Grafstrom RH, Cox S, et al. Quinazolines as cyclin dependent kinase inhibitors. Bioorganic & Medicinal Chemistry Letters. 2001;11(9):1157-60.

Nour A, Hayashi T, Chan M, Yao S, Tawatao RI, Crain B, et al. Discovery of substituted 4-aminoquinazolines as selective Toll-like receptor 4 ligands. Bioorganic & Medicinal Chemistry Letters. 2014;24(21): 4931-38.

Varadi A, Horváth P, Kurtán T, Mándi A, Tóth G, Gergely A, et al. Synthesis and configurational assignment of 1,2-dihydroimidazo[5,1-b]quinazoline-3,9- diones: novel NMDA receptor antagonists. Tetrahedron. 2012;68(50):10365-71.

Nepomuceno GM, Chan KM, Huynh V, Martin KS, Moore JT, O’Brien TE, et al. Synthesis and evaluation of quinazolines as inhibitors of the bacterial cell division protein FtsZ. ACS Medicinal Chemistry Letters. 2015;6(3):308-12.

Hassanein HH, El Nahal HM, Gerges FR. Synthesis of some non-antimonial compounds bioisosteric to praziquantel. European Journal of Medicinal Chemistry. 1995;30(6):525-9.

Stefanov AV. Preclinical studies of drugs. Guidelines [Доклінічні дослідження лікарських засобів. Методичні рекомендації]. Kyiv: Avitsenna; 2001. Ukrainian.

Obushak ND, Matiichuk VS, Vasylyshin RYa, Ostapyuk YuV. Heterocyclic syntheses on the basis of arylation products of unsaturated compounds: X. 3-Aryl-2-chloropropanals as reagents for the synthesis of 2-amino-1,3-thiazole derivatives. Russ J Org Chem. 2004;40(3):383-9.

Yarovenko VN, Kosarev SA, Zavarzin IV, Krayushkin MM. Reactions of monothiooxamides with N-nucleophiles. Synthesis of 4,5-dihydroiidazole-2-carboxanilides. Russ. Chem. Bull. 1999;48(4):749-53.

Gatsura VV. Methods primary pharmacological studies of biologically active substances [Методы первичного фармакологического исследования биологически активных веществ]. Moscow: Medicine; 1974. Russian.

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Published

2018-06-21

How to Cite

Horishny, V. Y., Frolov, D. A., Nektegayev, I. O., Ostapiuk, Y. V., & Matiychuk, V. S. (2018). SYNTHESIS AND PRIMARY SCREENING OF ANTI-INFLAMMATORY ACTIVITY OF 1,4,5,6-TETRAHYDROPYRIMIDINE-2-CARBOXAMIDES. Pharmaceutical Review Farmacevtičnij časopis, (2), 5–10. https://doi.org/10.11603/2312-0967.2018.2.9125

Issue

No. 2 (2018)

Section

Synthesis of biologically active compounds

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