SYNTHESIS OF 2,6-DIAMINO-5-HETARYLPYRIMIDINES AS POTENTIAL ANTIFOLATES: УДК 547.853.7

D. Milokhov; O. Khilya; Yu. Volovenko

Автор(и)

D. Milokhov, PhD-Student Київський національний університет імені Тараса Шевченка
O. Khilya, PhD Київський національний університет імені Тараса Шевченка
Yu. Volovenko, Professor Київський національний університет імені Тараса Шевченка

Ключові слова:

antifolate agents, diaminopyrimidines, 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles

Анотація

The ring transformation reactions of 2-hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles with guanidine as 1,3-N,N-binucleophiles have been investigated. The method allows obtaining diaminopyrimidines, which have been of great interest in recent years due to their potent biological and pharmacological properties.

Посилання

1. Kompis I. M. DNA and RNA Synthesis: Antifolates / I.M. Kompis, K. Islam, R.L. Then // Chem. Rev. – 2005. – Vol. 105. – Р. 593–620.

2. Structure-based design, synthesis and preliminary evaluation of selective inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis / M.H.R.I. El-Hamamsy, A.W. Smith, A.S. Thompson, M.D. Threadgill // Bioorg. Med. Chem. – 2007. – Vol. 15 – P. 4552–4576.

3. Algul O. 2,4-Diamino-5-(2-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition / O. Algul, J.L. Paulsen, A.C. Anderson // J. Mol. Graph. Modelling. – 2011. – Vol. 29. – P. 608–613.

4. Design, synthesis, biological evaluation and computational investigation of novel inhibitors of dihydrofolate reductase of opportunistic pathogens / S. Bag, N.R. Tawari, M.S. Degani, S.F. Queener // Bioorg. Med. Chem. – 2010. – Vol. 18. – P. 3187–3197.

5. Synthesis of 2-(2-hetaryl)-6-hydroxy-3-(R-amino)-2-hexenenitriles / O. V. Khilya, T. A. Volovnenko, A. V. Turov [et al.] // Chem. Heterocycl. Compd. – 2013. – Vol. 48. – P. 1770–1780.

6. A ring opening reaction of 2-hetaryl-2-(tetrahydro-2-furanylidene) acetonitriles with amino acids / O. V. Khilya, D. S. Milokhov, V. Yu. Postupalenko [et al.] // Monatsh. Chem. – 2013. – Vol. 144. – P. 1071–1079.

7. Reaction of 2-Hetaryl-2-(tetrahydro-2-furanyliden)acetonitriles with 1,3-N,N-Binucleophiles / D.S. Milokhov, O.V. Khilya, Yu.M. Volovenko [et al.] // Synlett. – 2012. – Vol. 23. – P. 2063–2068.

8. Patzel M. Ring transformation reactions of bridged 1,3-dicarbonyl heteroanalogs as a versatile entry to side chain functionalized alkylheterocycles / M. Pätzel, J. Liebscher // Synthesis. – 1995. – P. 879–894.

9. Neidlein R. Synthesis of 1,2,4-oxadiazole substituted pyrazole, isoxazole and pyrimidine heterocycles / R. Neidlein, S. Li // J. Heterocycl. Chem. – 1996. – Vol. 33. – P. 1943–1949.

10. Synthesis of 2-hetaryl-2-(tetrahydrofuran-2-yliden)acetonitriles / O.V. Khilya, T. A. Volovnenko, A. V. Turov [et al.] // Chem. Heterocycl. Compd. – 2011. – Vol. 47. – P. 1141–1154.