M. A. Iradyan

Antitumor activity of imidazole derivatives: dacarbazine and the new alkylating agent imidazene (Review)

The physicochemical properties and antitumor activity of dacarbazine, its analogs, and the new alkylating agent imidazene are reviewed. It is shown that the activity of dacarbazine is superior to most of its analogs. Imidazene exhibits an advantage over dacarbazine with respect to both stability and activity and can be used for the treatment of malignant melanoma and sarcoma of soft tissues and in combined chemotherapy.

Imidazole derivatives and their antitumor activity (review)

Bis(2-chloroethyl)amino derivatives of imidazole, 4(5)-aminoimidazol-5(4)-carboxamide, 4-nitro-5-thioimidazole, benzimidazole, and imidazolylpeptides are reviewed. Data are presented for active compounds, some of which have passed the preclinical testing stage. Structures under consideration are interesting with respect to both the search for new antitumor drugs and the synthesis of compounds with different biological properties.

Imidazole Derivatives. XXIX. Synthesis and Biological Activity of Thiosemicarbazides and Hydrazonohydrazides of 4-Nitroimidazole-5-thioacetic Acids

Previously [1 – 3], we reported on S-substituted 1-benzyl-4-nitro-5-thioimidazoles possessing antitumor, mutagen, and antimutagen properties. In continuation of these investigations, we have synthesized a series of 4-methylthiosemicarbazides V and hydrazonohydrazides VI based on 1-methyland 1-benzyl-4-nitroimidazole-5thioacetic acid hydrazides (IV). The initial esters II and acids III were obtained from ammonium mercaptides I. Then, ethyl esters II were converted into hydrazides IV and the target 4-mehylthiosemicarbazides V were obtained via reactions of these hydrazides with methylisocyanate. R = CH3 (Ia – Va, Ib – Vb), (4-CH3O)(3-NO2)C6H3CH2 (Ic – Vc), (4-C5H11O)(3-NO2)C6H3CH2 (Id, IId, IVd, Vd); R = H (Ia – Va), CH3 (Ib – Vb, Ic – Vc, Id, IId, IVd, Vd). The target hydrazonohydrazides VI were obtained via condensation of hydrazides IV with the corresponding 4-fluoro-, 4-amyloxy-, and 4-amyloxy-3-nitroacetophenones.

Imidazole derivatives XVIII. Synthesis and antitumor activity of some bis[2-chloroethyl]amino imidazole derivatives

T h e 1 b e n z y l s u b s t i t u t e d i m i d a z o l e s ( I V g a n d h ) w e r e o b t a i n e d b y t h e a l k y l a t i o n o f t h e i s o d i u m s a l t o f 4 ( 5 ) ( 4 a c e t y l a m i n o p h e n y l ) i m i d a z o l e w i t h b e n z y l c h l o r i d e w i t h s u b s e q u e n t d e a c e t y l a t i o n o f t h e 1 b e n z y l 4 ( 4 a c e t y l a m i n o p h e n y l ) i m i d a z o l e s .

Synthesis and antibacterial activity of 2-hydrazino5-bromomethyl-4,5-dihydrothiazole hydrazones

A series of 2-hydrazino-5-bromomethyl-4,5-dihydrothiazole hydrazones based on substituted N4-allylthiosemicarbazones was synthesized. Some of these hydrazones were found to have moderate antibacterial activity against Staphylococcus aureus 209P, 1 and Shigella flexneri.

Imidazole Derivatives. XXVIII. Synthesis and Antitumor Activity of 4(5)-[4-(3,3-Dimethyl-1-triazeno)-3-nitrophenyl]imidazole and Related Compounds

The dimethyltriazeno group, possessing alkylating properties, can be used in the synthesis of new antitumor compounds. For example, 4(5)-[(3,3-dimethyl-1-triazeno)imidazole-5(4)-carboxamide (decarbazin) is used in the combined chemotherapy of malignant melanoma, Hodgkin’s disease, and osteogenic and fibrous sarcomas under clinical conditions [1 – 4]. A significant disadvantage of this compound is its instability. As is known, 1-phenyl-3,3-dimethyltriazenes are stable compounds also possessing antitumor properties [5, 6]. Phenyltriazenes were reported to exhibit antimetastatic activity as well [7, 8]. Proceeding from these considerations, we synthesized a series of dimethyltriazenophenylimidazoldes (I – VI) based on 4(5)-(4-aminophenyl)imidazole derivatives:

Synthesis and Antibacterial Activity of 3,6-Diaryl-7H-[1,2,4]Triazolo[3,4-b][1,3,4]Thiadiazines

Interaction of 4-amino-5-(2-alkoxyphenyl)-4H-[1,2,4]triazole-3-thiols with substituted phenacyl bromides was used to synthesize 6-(2′-alkoxyphenyl)-3-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines. Biological studies identified an interaction between chemical structure and antibacterial activity in this series of triazolothiadiazines.

Synthesis and Antibacterial Activity of 5-Thiomethylfuran-2-Carboxylic Acid Derivatives

We report here the synthesis of methyl esters of 5-(1H-1,2,4-triazol-3-ylsulfanylmethyl)furan-2-carboxylic acids containing an alkyl or 2(4)-alkoxyphenyl substituent in position 5 of the triazole ring. Alkaline hydrolysis of these esters yielded the corresponding acids. X-ray diffraction studies showed that the oscillating hydrogen atom in the triazole ring of the methyl ester of 5-[5-(2-ethoxyphenyl)-1H-1,2,4-triazol-3-ylsulfanylmethyl] furyl-2-carboxylic acid was located on the N1 atom. The antibacterial properties of the esters and acids were studied.