Regioselective N-alkylation of some imidazole-containing heterocycles and their in vitro anticancer evaluation

Karaaslan C., DOĞANÇ F., ALP M., KOÇ A., KARABAY A. Z., GÖKER A. H.

JOURNAL OF MOLECULAR STRUCTURE, cilt.1205, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1205
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.molstruc.2019.127673
  • Dergi Adı: JOURNAL OF MOLECULAR STRUCTURE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: Imidazo[4,5-b]pyridine, Imidazo[4,5-c]pyridine, imidazo[4,5-d]pyrimidine (purine), Imidazo[4,5-b]pyrazine, Regioisomer, NOESY (nuclear overhauser effect spectroscopy), DERIVATIVES, POTENT, INHIBITORS, DISCOVERY, SERIES, IDENTIFICATION
  • Ankara Üniversitesi Adresli: Evet

Özet

Imidazole-containing heterocycles: Imidazopyridines, imidazopyrimidines and imidazopyra-zines can exist more tautomeric forms than benzimidazoles. Their regioselectivities were determined for N-alkylations with 4-fluorobenzyl bromide under basic conditions (K2CO3) in DMF. We observed that, regioisomers were mainly formed as a mixture in this reaction and N-benzylation occurs at a higher ratio on six membered heterocycles. Their structural assignments were made with the use of two-dimensional H-1-H-1 NOE (nuclear overhauser effect spectroscopy, NOESY). Complementary structural informationwas provided by 2D-HMBC spectra of the compounds. Synthesized compounds were tested for in vitro cytotoxic activities against Human colon cancer cell line (HCT-116) and leukemia cell lines (K562 and HL-60) by MTT test. Among them, imidazopyridine analogue 10, bearing bromine atom at the C-6 position of the pyridine moiety, gave the lowest IC50 value with 6-7 mu g/mL against all three cancer cell lines. (C) 2020 Elsevier B.V. All rights reserved.