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. // MACROHETEROCYCLES. - 2016. - V. 9, l. 3. - P. 301-306.

ISSN/EISSN:

1998-9539 / нет данных

Type:

Article

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.

Author keywords:

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

DOI:

10.6060/mhc160213o

Web of Science ID:

ISI:000389761400015

Соавторы в МНС:

Другие поля

Поле	Значение
Publisher	IVANOVO STATE UNIV CHEMICAL TECHNOLOGY
Address	FRIEDRICH ENGELS AV., 7, IVANOVO, RF-153000, RUSSIA
Language	Russian
Keywords-Plus	RECEPTOR ANTAGONISTS; INHIBITORS; POTENT
Research-Areas	Chemistry
Web-of-Science-Categories	Chemistry, Multidisciplinary
Author-Email	iov@ios.uran.ru
Number-of-Cited-References	29
Usage-Count-Last-180-days	3
Usage-Count-Since-2013	6
Journal-ISO	Macroheterocyles
Doc-Delivery-Number	EE6YV