V. S. Brovarets

Reaction of 7-phenyl-7H-pyrazolo-[3,4-d][1,2,3]triazin-4-ol with thionyl chloride

The reaction of 7-phenyl-7H-pyrazolo[3,4-d][1,2,3]triazin-4-ol with thionyl chloride has been studied in the presence and absence of dimethyl formamide. It was found that heating the compound with thionyl chloride in the absence of dimethyl formamide gave 5-amino-1-phenyl-1H-pyrazole-4-carboxylic acid chloride and in its presence a mixture of 5-chloro-N-formyl-1-phenyl-1H-pyrazole-4-carboxamide, 5-chloro-1-phenyl-1H-pyrazole-4-carboxamide, and 4-chloro-6-(5-chloro-1-phenyl-1H-pyrazol-4-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine.

Conversions of 7-aryl-7H-pyrazolo[3,4-d]-[1,2,3]triazin-4-ols by the action of phosphorus pentoxide, pentasulfide, and oxychloride

The interaction of 7-aryl-7H-pyrazolo[3,4-d][1,2,3]triazin-4-ols with phosphorus pentoxide or pentasulfide leads to the formation of 6-(5-amino-1-aryl-1H-pyrazol-4-yl)-1-aryl-1H,4H-pyrazolo[3,4-d][1,3]oxazin-4-ones and 6-(5-amino-1-aryl-1H-pyrazol-4-yl)-1-aryl-1H,4H-pyrazolo[3,4-d][1,3]thiazine-4-thiones, respectively. Reaction with phosphorus oxychloride leads to 1-aryl-5-chloro-1H-pyrazole-4-carbonyl chlorides, from which the corresponding amides, hydrazides, and substituted 1,3,4-oxadiazoles were synthesized.

Introduction of chiral 2-(aminoalkyl) substituents into 5-amino-1,3-oxazol-4-ylphosphonic acid derivatives and their use in phosphonodipeptide synthesis

Starting from phthalimidoalkanoylamines 1 (amino-protected derivatives of L-alanine, L-valine, and L-leucine), we have suggested a straightforward synthetic route to 5-amino-1,3-oxazol-4-ylphosphonic acid derivatives 5 containing a chiral aminoalkyl substituent on the 2-position of the oxazole ring. Compounds 5 have been further used to obtain phosphonodipeptides 8, 9, and 10 with the original optical purity retained.

Synthesis of 4-alkyl-2-aryl-1,3-oxazole[5,4-d]pyrimidine-7(4H)-thiones and 6-alkyl-2-aryl-1,3-oxazole[5,4-d]pyrimidin-7(6H)-ones from 2-aroylamino-3,3-dichloroacrylonitriles

The sequential treatment of accessible 2-aroylamino-3,3-dichloroacrylonitriles with excess of amine, triethyl orthoformate, and hydrogen sulfide results in 4-substituted oxazole[5,4-d]pyrimidine-7(4H)-thione. The sequential reactions of the same reagents with sodium methylate, trifluoroacetic acid, triethyl orthoformate, and amines give rise to the 6-substituted oxazole[5,4-d]pyrimidin-7(4H)-one.

1,3-Oxazole derivatives as potential anticancer agents

Microtubules play a significant role in cell growth and functioning. Therefore inhibition of the microtubule assemblies has emerged as one of the most promising cancer treatment strategies. Predictive QSAR models were built on a series of selective inhibitors of the tubulin were performed by using Associative Neural Networks (ANN). To overcome the problem of data overfitting due to the descriptor selection, a 5-fold cross-validation with variable selection in each step of the analysis was used. All developed QSAR models showed excellent statistics on the training (total accuracy: 0.96-0.97) and test sets (total accuracy: 0.95-97). The models were further validated by 11 synthesized 1,3-oxazole derivatives and all of them showed inhibitory effect on the Hep-2 cancer cell line. The most promising compound showed inhibitory activity IC50=60.2μM. In order to hypothesize their mechanism of action the top three compounds were docked in the colchicine binding site of tubulin and showed reasonable docking scores as well as favorable interactions with the protein.

Synthesis of 2,5-di(hydroxyalkyl)-1,3-thiazoles

A general approach towards synthesis of 2(5)-hydroxyalkyl-substituted 1,3-thiazole derivatives has been proposed. The method includes lithiation of 1,3-thiazole ring followed by reacting the formed thiazole lithium derivatives with electrophiles.

Reaction of 2-Aryl-4-Cyano-1,3-Oxazole-5-Sulfonyl Chlorides With 5-Amino-1H-Pyrazoles and 5-Amino-1H-1,2,4-Triazole

The reaction of 2-aryl-4-cyano-1,3-oxazole-5-sulfonyl chlorides with 5-amino-3-R-1H-pyrazoles and 5-amino-1H-1,2,4-triazole gave 5-[(3-R-5-amino-1H-pyrazol-1-yl)sulfonyl]-2-aryl-1,3-oxazole-4-carbo- nitriles and 5-[(5-amino-1H-1,2,4-triazol-1-yl)sulfonyl]-2-aryl-1,3-oxazole-4-carbonitriles. The action of sodium hydride on these carbonitriles leads to the elimination of sulfur dioxide and cyclocondensation to give new heterocyclic systems, namely, [1,3]oxazolo[5,4-d]pyrazolo[1,5-a]-pyrimidine and [1,3]oxazolo[5,4-d][1,2,4]triazolo[1,5-a]pyrimidine.

SYNTHESIS OF NOVEL PYRAZOLO(3,4-d)(1,2,3)TRIAZINES

Studies have been conducted of the reactions of 7-phenyl-3,7-dihydro-4H-pyrazolo[3,4-d]-[1,2,3]triazin-4-one with alkyl halides and formaldehyde, that occurred with retention of the pyrazolotriazine structure. Ethyl 2-(4-oxo-7-phenyl-4,7-dihydro-3H-pyrazolo[3,4-d][1,2,3]triazin-3-yl)-acetate was prepared by the reaction of 7-phenyl-3,7-dihydro-4H-pyrazolo[3,4-d][1,2,3]triazin-4-one with ethyl chloroacetate. It was used to synthesize the corresponding hydrazide with the aim of introducing the pyrazole or 1,3,4-oxadiazole fragments in the side chain of a bicyclic system.

Interaction of 2-aryl-4-cyano-1,3-oxazole-5-sulfonyl chlorides with amidines

Reaction of 4-cyano-1,3-oxazole-5-sulfonyl chlorides with amidines results in new 7-amino-1,3-oxazolo[5,4-d]pyrimidines. Their structure was confirmed by spectral methods and X-ray diffraction analysis.

Reaction of diethyl 1-acylamino-2,2-dichloroethenylphosphonates with amino acids esters

Reactions of available diethyl 1-acylamino-2,2-dichloroethenylphosphonates with amino acids esters were studied, which in the case of esters of proline, nipecotic and isonipecotic acids resulted in N-substituted derivatives of 5-amino-4-diethoxyphosphoryloxazol in high yields. Their behavior in the acidic and alkaline media was investigated by the example of methyl N-(4-diethoxyphosphoryl-2-R-oxazol-5-yl)isonipecotinate.