Alexander V. Mazepa

Synthesis, structure and affinity of novel 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones for CNS central and peripheral benzodiazepine receptors

A series of novel 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones (7-15) was synthesized and their in vitro affinity for both the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor (PBR) of rat brain was studied. Racemic mixture of 7-bromo-3-(2-methoxy)ethoxy-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one (13) was separated into enantiomers 14, 15 by chiral HPLC. Absolute configuration of R-enantiomer 15 was determined by the method of X-ray diffraction analysis. The affinity of S-enantiomer 14 for CBR ( IC50)=245 nM) is 20-fold higher than the affinity of R-enantiomer 15 (IC50)=4,930 nM). A high selectivity for CBR versus PBR (IC50) (PBR)>10,000 nM) was shown by all reported compounds. Compound 12 was revealed as a potent (IC50)=9 nM) and selective CBR ligand among the synthesized 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones.

Chiral ureas with two electronegative substituents at 1-N: An unusual case of coexisting pyramidal and almost planar 1-N atoms in the same crystal†

XRD studies of structure of N-acetoxy-N-methoxyurea and N,N-bis(methoxycarbonyl)-N-methoxyimide have revealed that in N-methoxy-N-X-ureas (X = OAc, Cl, OMe, N(+)C(5)H(5)) the additional shortening of N-OMe bond took place, which arising from an n(O(Me))-sigma*(N-X) anomeric orbital interaction. XRD studies of N-chloro-N-ethoxyurea crystal have revealed the presence of two kinds of anomeric nitrogen configuration in the O-N-Cl group in the form of a pyramidal configuration and a planar configuration for same 1-N nitrogen atom. XRD studies of N-4-chlorobenzoyloxy-N-ethoxyurea have revealed that the degree of pyramidality of the 1-N nitrogen in N-aroyloxy-N-alkoxyureas is tuned by orientation of benzoyl group with respect to the N-O bond, which in turn depends of size of N-alkoxy group.

Synthesis and Conformational Characteristics of Benzyl-Substituted p-tert-Butylcalixarenes

Abstract(m-Methylbenzyloxy)-, bis(p-methylbenzyloxy)-, and bis(m-methylbenzyloxy)-p-tert-butylcalix[4]arenes were prepared by reactions of p-tert-butylcalix[4]arene with p- and m-methylbenzyl bromides in the presence of alkali metal carbonates. Silylation of these derivatives gave (m-methylbenzyloxy)bis(trimethylsilyloxy)-, bis(m-methylbenzyloxy)bis(trimethylsilyloxy)-, and bis(p-methylbenzyloxy)bis(trimethylsilyloxy)-p-tert-butylcalix[4]arenes. With phase-transfer catalysis, bis(p-methylbenzyloxy)bis(2-propenyloxy)- and bis(m-methylbenzyloxy)bis(2-propenyloxy)-p-tert-butylcalix[4]arenes were obtained. Alkylation of the monosubstituted calixarene yields the corresponding trisubstituted derivative.

Dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide – a versatile building block for the synthesis of new thiopyran-based heterocyclic systems

Three series of new cyclic sulfones have been prepared by a one-pot multi-component reaction (MCR) starting from the readily available dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide. The in silico screening of the synthesized compounds revealed their high anti-inflammatory, antiarthritic, antiasthmatic and antiallergic potential coupled with the strong probability levels of cystinyl aminopeptidase inhibition. The key structures were confirmed by 2D NMR techniques.

New ylidene and spirocyclopropyl derivatives of cholestanone and dehydroepiandrosterone series and their ability to induce cholesteric mesophase in nematic solvent

ABSTRACT New ylidene and spirocyclopropyl derivatives of cholestanone and dehydroepiandrosterone series were synthesized and their structure was determined by X-ray analysis. These compounds may be used as chiral dopants for cholesteric liquid crystal compositions which are applied in bistable displays with low power consumption. The ability of the synthesized substances to induce cholesteric mesophase in 4′-pentyl-1,1′-biphenyl-4-carbоnitrile nematic solvent was examined. The highest values of the helical twisting power |β| (190.0 ± 2.3) and (165.5 ± 1.9) µm−1 mol pats−1 were showed by (E)-2-{[3-(1,1′-biphenyl-4-yl)-1-phenyl-1H-pyrazol-4-yl]methyldene}-cholestanon and (1S,2S)-1-(1-phenyl-3-(4-methoxyphenyl)-1H-pyrazole-4-yl)-2,16′-spirocyclopropyldehydroepiandrosterone, correspondingly. GRAPHICAL ABSTRACT

Pictet–Spengler reaction in the synthesis of condensed benzodiazepines: synthesis of 11-hetaryl derivatives of 11,12-dihydroquinazolino[3,2-c][2,3]benzodiazepin-14(6H)-ones

New derivatives of 11,12-dihydroquinazolino[3,2-c][2,3]benzodiazepin-14(6H)-one have been synthesized. 11-(2-Thienyl)- and 11-(5-R-2-furyl)-substituted compounds were prepared by the Pictet–Spengler reaction of 3-amino-2-(3,4-dimethoxybenzyl)quinazolin-4(3H)-one with heterocyclic aldehydes in aprotic media. Their chemical structures were confirmed by 1H and 13C NMR spectroscopy and mass spectrometry. We observed the opening of diazepine ring in 8,9-dimethoxy-11-(5-chloro-2-furyl)-11,12-dihydroquinazolino[3,2-c][2,3]benzodiazepin-14(6H)-one when treated with trifluoroacetic acid, and the structure of the product was determined by NMR (1H, 13C, HSQC, HMBC experiments) and mass spectrometry data. The crystal structure of 3-amino-2-[4,5-dimethoxy-2-[(5-oxofuran-2(5H)-yliden)methyl]benzyl]quinazolin-4(3H)-one was confirmed by single-crystal X-ray analysis.Graphical abstract