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A three-component organocatalytic reaction of 1,3-dipolar cycloaddition between the in situ generated azomethine ylides and 3-substituted 1,2-diphenylcyclopropenes is described. The azomethine ylides have been generated via condensation of aromatic compounds (such as isatins and acenaphthenequinone) with benzylamines. The reaction has afforded derivatives of 3-azabicyclo[3.1.0]hexane, spiro-fused with the fragments of 2-oxindole and acenaphthylene-1(2H)-one. The cycloadducts have been obtained with yield up to 91%, mainly as individual diastereomers. The influence of bifunctional squaramide-based organocatalysts on the course of these three-component reactions has been investigated. Antiproliferative activity of selected synthesized compounds with respect to the human erythromyelosis (K562) and melanoma (Sk-mel-2) cell lines has been assessed in vitro by means of MTS analysis. [ABSTRACT FROM AUTHOR]

Cyclocondensation of α-acylacetamidine with 2-methylsulfanyl-4,6-dichloropyrimidine-5-carbaldehyde proceeds chemo- and regioselectively involving replacement by the α-carbon of the amidine of the chlorine in the aromatic ring and a reaction of the amino group with the formyl group. [ABSTRACT FROM AUTHOR]

The direction of the cyclocondensation of 2-fluoro-5-nitrobenzaldehyde with five amidines having α-hydrogen atoms has been studied. It was established that depending on the structure of the amidine the main products of the reaction may be not only quinazolines but also 3-aminoisoquinolines. A new convenient route has been found for the synthesis of 3-aminoisoquinolines consisting of the cyclocondensation of α-acylacetamidines with 2-fluoro-5-nitrobenzaldehyde. [ABSTRACT FROM AUTHOR]

Reactions of diaminoacrylic acid derivatives (I) with (het)aromatic nitriles containing a labile halogen atom in the o-position provides access to fused diaminoazides via the intermediacy of the chlorine substitution products. [ABSTRACT FROM AUTHOR]

4-Methyl-substituted 6-oxa-8α-analogs of steroid estrogens have been synthesized and the 1H and 13C NMR signals of these compounds have been completely assigned. It is shown that introduction of a methyl group in position 4 of steroids of the given stereochemical series leads to the loss of uterotropic and hypertriglyceridemic effects of the modified compounds. Steroids with these properties may have promise for the creation of vectors for transport into target organs of estrogens of other classes of compounds and inhibitors of enzymes responsible for the metabolism of hormones. [ABSTRACT FROM AUTHOR]

Thermolysis of dimethyl esters of stereoisomeric phthalimidoaziridine-2,3-dicarboxylic acids in the presence of dimethyl fumarate, dimethyl maleate, and N-phenylmaleimide occurred stereo-specifically and stereoselectively led to the formation of derivatives of 1-phthalimidopyrrolidine, products of 1,3-dipolar additrion of intermediately arising azomethine ylides. In keeping with the rules of the conservation of orbital symmetry the thermal opening of the 2,3-disubstituted 1-phthalimidoaziridines into azomethine ylides occurred conrotatory. The relative positions of the substituents in the dipolarophiles is retained in the reaction products indicating the concerted addition mechanism. [ABSTRACT FROM AUTHOR]

The reaction of 3(5)-amino-5(3)-methylpyrazole with hexafluoroacetylacetone depending on the process conditions led to the formation either of pyrazolo[1,5- a]pyrimidine or pyrazolo[3,4- b]-pyridine. By means of 2D NMR spectroscopy the structure was established of a stable intermediate product, 2-methyl-5,7-bis(trifluoromethyl)-4,5,6,7-tetrahydropyrazolo[1,5- a]-pyrimidine-5,7-diol, whose dehydration yielded the above compounds. [ABSTRACT FROM AUTHOR]

Cyclocondensation of N-substituted 5-aminopyrazoles with fluorinated 1,3-diketones yielded 4-trifluoromethyl-substituted pyrazolo[3,4- b]pyridines as the only reaction products. The regiostructure of compounds obtained was proved by 1H and 13C NMR homo- and heteronuclear correlation spectroscopy. Characteristic chemical shifts in the 13C NMR spectra of regioisomeric pyrazolo[3,4- b]pyridines were established. [ABSTRACT FROM AUTHOR]

Stereoselectivity of reaction with Raney nickel of D-homoestra-1,3,5(10),8,14-pentaenes containing one or two methyl groups in position 16 was investigated. The reaction direction is governed by the orientation of the substituent at C17a. The signals in the 1H and 13C NMR spectra of four synthesized compounds were completely assigned. Criteria for evaluation of the character of rings junction in analogs of D-homoequilenine were suggested. 16,16-Dimethyl-3-methoxy-D-homo-13α-estra-1,3,5(10),6,8-pentaen-17a-one was subjected to X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Presents the results of a clinical study on the divergence of de novo biosynthesis of inosine-5'-triphosphate. Chemical structure of 5-aminoimidazole ribonucleotide; Decarboxylation of 5-amino-4-carboxy-imidazole ribonucleotide in the absence of enzyme; Classification of the enzyme isolated from human erythrocytes.

Modified equilenin analogs were synthesized with a view to examine the relation between the structure and biological properties of steroid estrogens. The 1H and 13C NMR signals of six estra-1,3,5,7,9-pentaenes were completely assigned using homo- and heteronuclear correlation NMR spectroscopy. The structure of equilenin methyl ester was determined by X-ray analysis. Among the synthesized steroids, compounds were found which exhibit hypocholesterinemic activity with no uterotropic and hypertriglyceridemic effects. [ABSTRACT FROM AUTHOR]

Cyanoethylation of natural glycyrrhetic acid methyl ester gave the corresponding 3β-O-(2-cyanoethyl) derivative which was treated with sodium azide to obtain a novel tetrazolyl derivative of biologically active triterpenoid, methyl 3β-[2-(1H-tetrazol-5-yl)ethoxy]-11-oxoolean-12-en-30-oate. [ABSTRACT FROM AUTHOR]

A new semisynthetic derivative of natural taraxerone fused to a pyrazine ring through the C2-C3 bond, (4aR,6bR,14aR,16aS)-2,2,4a,6b,9,9,14a,16a-octamethyl-1,2,3,4,4a,5,6b,7,8,8a,9,14,14a,14b,15,16,16a,16boctadecahydrochryseno[1,2-g]quinoxaline, has been synthesized by the Willgerodt-Kindler reaction, and its structure was determined by X-ray analysis and NMR spectroscopy. [ABSTRACT FROM AUTHOR]

In order to estimate the potential of steroid estrogens modification, three D-homoanalogs of estrogens have been prepared; their structures and biological properties have been studied. The expansion of D-ring in such compounds has lead to strong decrease if the uterotropic action, however, the unfavorable hypertriglyceridemic effect has been retained. The latter has been eliminated by combined action of the studied steroids and ursolic acid; therewith the hypocholesterolemic activity has been retained. [ABSTRACT FROM AUTHOR]

Aiming at the investigation of the mechanism of functioning of steroid estrogens a series of compounds with unnatural rings junction was synthesized. All investigated compounds exhibit a reduced uterotropic activity. It was established applying the NMR spectroscopy that 7α-methyl-3-methoxy-D-homo-6-oxa-8α,14β-estra-1,3,5(10)-trien-17a-one existed in solution in two conformations distinguished by the structure of the rings B, C, and D simultaneously. The reaction of 17-methylidene-3-methoxy-6-oxa-8α-estra-1,3,5(10)-triene with hydrobromic acid in acetic acid promotes a rearrangement with the migration of a methyl group into the position 17 resulting in the formation of 17,17-dimethyl-6-oxa-8α-gona-1,3,5(10),13(14)-tetraene derivatives. [ABSTRACT FROM AUTHOR]

Thermally induced opening of the diaziridine ring at the carbon-nitrogen bond in unsymmetrically substituted 6-aryl-1,5-diazabicyclo[3.1.0]hexanes is characterized by low regioselectivity which is likely to be determined by the inductive effect of substituents in the trimethylene bridge. 1,3-Dipolar cycloaddition of the resulting azomethine imines to phenyl isocyanate is regioselective: it occurs at the double carbon-nitrogen bond with predominant formation of the corresponding cis adducts due to dipolarophile approach to Z-azomethine imine at the sterically less hindered side. Analogous approach of dipolarophile is also observed in the reaction with N-arylmaleimides. [ABSTRACT FROM AUTHOR]

ording to the X-ray diffraction and NMR data, two D-homo-B-nor-8α-analogs of steroidal estrogens in crystal and in solution have similar conformations. The distances between hydrogen atoms in their molecules, calculated ab initio and by the PM3 and MM methods, correspond to those found experimentally. These results substantiated docking of the modified estrogens into ligand-binding pockets of various estrogen receptor isoforms with a view to search for compounds with improved biological properties. This was demonstrated using 17,17-dimethyl-D-homo-B-nor-8α-estrone as an example. [ABSTRACT FROM AUTHOR]

The distances between the protons of four 8α-analogues of steroid estrogens as determined by X-ray data are consistent with the calculated values obtained by ab initio, PM3 and MM+ methods, that can be used for docking of these stereochemical analogs onto α-estrogen receptors. [ABSTRACT FROM AUTHOR]

The oxidation of N-aminophthalimide with lead tetraacetate in the presence of 5-[( E)-2-arylethenyl]-3-(4-methylphenyl)-1,2,4-oxadiazoles and 5-(4-methylphenyl)-3-[ E)-2-phenyl-ethenyl]-1,2,4-oxadiazole led to the formation of the corresponding (3-aryl-1-phthalimidoaziridin-2-yl)-(4-methylphenyl)-1,2,4-oxadiazoles. In the reaction with 3,5-distyryl-1,2,4-oxadiazole a mixture was obtained of two regioisomeric monoadducts and a diadduct in the ratio 80 : 15: 5; at the use of 3 equiv of the aziridinating reagents only diadduct was isolated as a mixture of two diastereoisomers in the ∼3 : 2 ratio that were separated by recrystallization. [ABSTRACT FROM AUTHOR]

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A three-step procedure has been developed for the synthesis of 3,5-disubstituted methyl pyridazine-4-carboxylates from accessible 2,3-disubstituted 2-cyclopropenecarboxylates. In the first step, cyclopropene derivatives react with diazomethane to give adducts having 2,3-diazabicyclo[3.1.1]hex-2-ene structure. The regio- and stereoselectivity of the cycloaddition has been determined. The second step is isomerization of the bicyclic adducts into 1,4-dihydropyridazine derivatives by the action of sodium methoxide. Finally, oxidation with potassium permanganate yields the target pyridazine-4-carboxylates. [ABSTRACT FROM AUTHOR]

A letter to the editor about the use of estrone sulfatase inhibitors in the development of drugs for treating breast cancer is presented.