Dihydroazolopyrimidine crownophanes. Synthesis and tuberculostatic activity

I. G. Ovchinnikova, M. S. Valova, O. V. Fedorova, A. A. Tumashov, M. A. Kravchenko, I. D. Medvinsk′i, G. L. Rusinov, V. N. Charushin

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Azolo[1,5-a] pyrimidines are considered to be purine analogues and they form one of the most promising groups of biologically active compounds[1-16] in medicinal chemistry. One of the strategies enhancing biochemical activity of azolo[1,5-a] pyrimidines is introduction of functional groups responsible for solubility and transport into their pharmacophore nucleus.[1,16] In this study, we wish to report ultrasound-and microwave-assisted one-pot cascade synthesis of macroheterocyclic 1-phenyl-2-(21-phenyl-10,11,13,14,20,20a-hexahydro-4aH-dibenzo-[13,14: 8,9][1,4,7] trioxacyclotetradecino[11,10-e] azolo[1,5-a] pyrimidin-20-yl)-1-ethanones. US and MV irradiation of the reaction mixtures under alkaline catalysis was found to promote a significant reduction of the reaction times (from 35 to 2 hours) and shift of the equilibrium in favor of 6,7-dihydroazolo[1,5-a] pyrimidine crownophanes in excellent yields (from 18[24] to 75 %). The high regio and stereoselectivity of the (R, S, R)-macroheterocyclic diastereomer formation was established by means of X-ray crystallography, 1H NMR spectroscopy, as well as HPLC and preparative chromatography. The aq. DMF appeared to be an acceptable solvent for stabilization of the important template-assisted pseudo-cyclic complex of the chalcone podand in this synthesis. Introduction of the dibenzo-crown ether transport moiety into 6,7-dihydroazolo[1,5-a] pyrimidines proved to increase their tuberculostatic activity in order to MIC 3.15 mg/ml.

Translated title of the contributionДИГИДРОАЗОЛОПИРИМИДИНОВЫЕ КРАУНОФАНЫ. СИНТЕЗ И ТУБЕРКУЛОСТАТИЧЕСКАЯ АКТИВНОСТЬ
Original languageEnglish
Pages (from-to)301-306
Number of pages6
JournalMacroheterocycles
Volume9
Issue number3
DOIs
Publication statusPublished - 2016

Keywords

  • Chalcone podand
  • dihydroazolopyrimidine crownophanes
  • template-assisted cascade reactions
  • microwave synthesis
  • sonochemical reaction
  • tuberculostatic activity
  • RECEPTOR ANTAGONISTS
  • INHIBITORS
  • POTENT

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry

WoS ResearchAreas Categories

  • Chemistry, Multidisciplinary

GRNTI

  • 31.00.00 CHEMISTRY

Level of Research Output

  • VAK List

Cite this

Ovchinnikova, I. G., Valova, M. S., Fedorova, O. V., Tumashov, A. A., Kravchenko, M. A., Medvinsk′i, I. D., ... Charushin, V. N. (2016). Dihydroazolopyrimidine crownophanes. Synthesis and tuberculostatic activity. Macroheterocycles, 9(3), 301-306. https://doi.org/10.6060/mhc160213o
Ovchinnikova, I. G. ; Valova, M. S. ; Fedorova, O. V. ; Tumashov, A. A. ; Kravchenko, M. A. ; Medvinsk′i, I. D. ; Rusinov, G. L. ; Charushin, V. N. / Dihydroazolopyrimidine crownophanes. Synthesis and tuberculostatic activity. In: Macroheterocycles. 2016 ; Vol. 9, No. 3. pp. 301-306.
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Ovchinnikova, IG, Valova, MS, Fedorova, OV, Tumashov, AA, Kravchenko, MA, Medvinsk′i, ID, Rusinov, GL & Charushin, VN 2016, 'Dihydroazolopyrimidine crownophanes. Synthesis and tuberculostatic activity' Macroheterocycles, vol. 9, no. 3, pp. 301-306. https://doi.org/10.6060/mhc160213o

Dihydroazolopyrimidine crownophanes. Synthesis and tuberculostatic activity. / Ovchinnikova, I. G.; Valova, M. S.; Fedorova, O. V.; Tumashov, A. A.; Kravchenko, M. A.; Medvinsk′i, I. D.; Rusinov, G. L.; Charushin, V. N.

In: Macroheterocycles, Vol. 9, No. 3, 2016, p. 301-306.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Ovchinnikova, I. G.

AU - Valova, M. S.

AU - Fedorova, O. V.

AU - Tumashov, A. A.

AU - Kravchenko, M. A.

AU - Medvinsk′i, I. D.

AU - Rusinov, G. L.

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Ovchinnikova IG, Valova MS, Fedorova OV, Tumashov AA, Kravchenko MA, Medvinsk′i ID et al. Dihydroazolopyrimidine crownophanes. Synthesis and tuberculostatic activity. Macroheterocycles. 2016;9(3):301-306. https://doi.org/10.6060/mhc160213o