L. P. Sidorova

Synthesis of New Fluorinated Derivatives of Quinolinecarboxylic Acids

Ethyl esters of 1-(7-Z-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carbamoyl)-5-X-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids (X = H, F; Z = pyrrolidino-, piperidino-, hexamethylenimino-, morpholino-, thiomorpholino-) have been synthesized by the interaction of quinolone-3-carboxylic acid hydrazides with ethyl esters of 3-ethoxy-2-(polyfluorobenzoyl)acrylic acid . It was shown possible to cyclize intramolecularly the esters obtained with the formation of 1,3,4-oxadiazino[6,5,4-i,j]quinoline derivatives.

Pharmacologic Evaluation of Antidepressant Activity and Synthesis of 2-Morpholino-5-phenyl-6H-1,3,4-thiadiazine Hydrobromide

Substituted thiadiazines exert a reliable therapeutic effect in treating stress, and a schematic description of their ability to influence all aspects of a stress response has been depicted. This study was conducted to pharmacologically evaluate compound L-17, a substituted thiadiazine, (2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide) for possible anti-psychotic/antidepressant activity. Compound L-17 was synthesized by cyclocondensation of α-bromoacetophenone with the original morpholine-4-carbothionic acid hydrazide. Pharmacologic evaluations were conducted using methods described by E.F. Lavretskaya (1985), and in accordance with published guidelines for studying drugs for neuroleptic activity. Compound L-17 was evaluated for various possible mechanisms of action, including its effects on cholinergic system agonists/antagonists, dopaminergic neurotransmission, the adrenergic system, and 5-HT3 serotonin receptors. One or more of these mechanisms may be responsible for the beneficial effects shown by thiadiazine compounds in experiments conducted to evaluate their activity in models of acute stress and acute myocardial infarction.

Ambident properties of 4-substituted thiosemicarbazides in condensations with fluoroacetic acids

Abstract4-Substituted thiosemicarbazides react with di- and trifluoroacetic acids to give the corresponding 3-fluoroalkyl-4,5-dihydro-1,2,4-triazole-5(1H)-thiones. Condensation of 4,4-disubstituted thiosemicarbazides with trifluoroacetic acid leads to formation of 2-amino-5-trifluoromethyl-1,3,4-thiadiazoles.

SYNTHESIS AND ANTITUMOR ACTIVITY OF FLUORINATED DERIVATIVES OF (i,j)-ANNELATED QUINOLONES

Tri- and pentacyclic fluoroquinolones were synthesized by intramolecular cyclization of the corresponding 3-hydrazinopolyfluorobenzoylacrylates followed by substitution of fluorine atoms by amine residues. The antitumor activity of the resulting compounds was studied at the National Cancer Institute using cultures of 60 cell lines of nine groups, including leukemia, lung tumor, large intestine tumor, CNS tumor, melanoma, ovary tumor, renal tumor, prostate tumor, and breast tumor. Relationships between structure and antitumor activity were analyzed. In vivo experimental data from hollow fiber tests are presented for two derivatives.

Fluorine-containing heterocycles: XVI. Reactions of tetrafluorobenzoyl isothiocyanate with hydrazines and their derivatives

Fluorinated derivatives of 4H-1,3-benzothiazin-4-one, [1,2,4]triazolo[4,3-a]pyrimidine, [1,2,4]triazolo[3,4-b][1,3]benzazoles, and 1,5-dihydro-1,2,4-triazole-5-thione were synthesized by addition of hydrazines and their derivatives to tetrafluorobenzoyl isothiocyanate, followed by cyclization of intermediate thiosemicarbazides.

Reaction of fullerene C60 with 2-azido-4,6-diphenylpyrimidine

The first representative of the pyrimidine-substituted [60]fullereno[1,2-b]aziridines was synthesized by the reaction of fullerene C60 with 2-azido-4,6-diphenylpyrimidine. 2-(Azahomo[60]fullereno)-4,6-diphenylpyrimidine was found to be formed as a by-product. The electrochemical properties of the adducts were studied.

Fluorine-Containing Heterocycles: VIII. Transformations of 2-Polyfluorobenzoylacrylates Having a Thiosemicarbazide Fragment

Depending on the conditions, 3-(4-R-thiosemicarbazido)-2-polyfluorobenzoylacrylates can be converted into the corresponding potassium salts, [1,3,4]thiadiazino[6,5,4-ij]quinolines, and pyrazole or 1,3,4-thiadiazole derivatives.

Fluoro-containing Heterocycles: VI. New Derivatives of 1,3,4-Thiadiazino[6,5,4-i,j]quinoline

A series of new tricyclic fluoroquinolones was prepared by replacing fluorine atoms in derivatives of 2-R-8-Y-7-oxo-9,10-difluoro-7H-1,3,4-thiadiazino[6,5,4-i,j]quinoline-6-carboxylic acids. In acids and esters containing a hydrogen atom in position 8 occurred replacement of F10 by amine rests, and in compounds with a fluorine in position 8 was substituted either F8or F10 and F8depending on the amine character.

2-Thiomorpholino-5-Aryl-6H-1,3,4-Thiadiazine Hydrobromides and Their Ability to Inhibit Nonenzymatic Protein Glycosylation

Cyclocondensation of α-halogenacetophenones with an original 4-morpholine thiosemicarbazide was used to synthesize a group of new Captions: of the 1,3,4-thiadiazine group, containing a thiomorpholine fragment at position 2 of the thiadiazine ring. Two members of this group of compounds were found to produce effective inhibition of nonenzymatic protein glycosylation in an in vitro model system. These test results allow compounds containing phenyl and fluorophenyl fragments IIIa and IIIb to be recommended for further study in in vivo experiments.

Effect of a New Class of Compounds of the Group of Substituted 5R1, 6H2-1,3,4-thiadiazine-2-amines on the Inflammatory and Cytokine Response in Experimental Myocardial Infarction

This study investigated the effects of the L-17 compound of the group of substituted 5R1, 6H2- 1,3,4-thiadiazine-2-amines on the immune response and the plasma level of circulating cytokines in acute myocardial infarction (MI) in rats. The study was based upon experimental work which demonstrated the role of local and systemic inflammatory reactions in MI. Acute MI in rats was induced by left coronary artery coagulation. Histological study of the myocardium sections has been carried out at the 1(th) and 7(th) days of the experimental myocardial infarction. Serum activity of creatine phosphokinase (CPK), aspartate aminotransferase (AST), isoenzymes 1 and 2 and lactate dehydroge nase (LDH1-2) were investigated at days 1(st)and 7(th). ELISA analysis for plasma cytokine levels was performed using commercially available test kits following the manufacturers instructions. Biochemical analysis in animals with the administration of the L-17 compound after MI showed that the AST and CPK levels at days 5 and 7 of experiments did not differ significantly from the values of intact animals. In animals of the group with MI without the administration of the L-17 compound, the IL-1 level 8 times and the TNF level 7.8 times exceeded the normal indicators, while the use of L-17 compound in the therapy resulted in only 1.8 times increase of IL-1 level and 4.7 times increase of TNF level in comparison with the norm. Thus, the introduction of L-17 compound in case of experimental MI delays exudative/alternative phase of inflammation, accelerates granulocytic and decreased the inflammation and anti-inflammation interleukins level.