G. M. Stepanyan

SYNTHESIS AND ANTITUMOR ACTIVITY OF SOME DISUBSTITUTED 5-(3-METHYL-4-ALKOXYBENZYL)PYRIMIDINES

The initial reagents were (3-methyl-4-alkoxybenzyl)malonates (I) obtained by reaction of the corresponding 3-methyl-4-alkoxybenzyl chlorides with malonic ester in the presence of sodium ethylate; the procedure was analogous to that described in [2]. Subsequent cyclization of the substituted malonic esters I with thiourea or guanidine hydrochloride in anhydrous ethanol in the presence of sodium ethylate led to the formation of pyrimidines II or III. Here, an important factor is the amount of sodium ethylate. It was established that 2-mercapto- and 2-amino-4,6-dihydroxypyrimidines II and III can be obtained with high yields only if two or three equivalents of sodium ethylate, respectively, are employed. Pyrimidines II were converted into methylthio derivatives IV by reaction with methyl iodide in a methanol solution of potassium hydroxide. The purity and identity of compounds II – IV were checked by TLC. The proposed structures were confirmed by data of the IR, 1 H NMR, and mass spectroscopy.

Synthesis and Antibacterial Activity of 2-[2,2-Dimethyl-4(3-Trifluoromethylphenyl)-Tetrahydropyran-4-Yl]Arylamine Oxalates

Interaction of ethylcyano(2,2-dimethyltetrahydro-2H-puran-4-yl)acetate with 3-trifluoromethylphenylmagnesium bromide yielded cyanoesters, decarbethoxylation of which produced the corresponding nitrile. Reduction of the latter with LiAlH4 led to the formation of 2-[2,2-dimethyl-4-(3-trimethylphenyl)tetrahydropyran-4-yl]ethylamine. Interaction of the resulting amine with aromatic aldehydes produced azomethines, which were reduced with NaBH4 to secondary amines, which were then converted to the oxalates. Several of these were found to have high levels of antibacterial activity.

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.

Arylsulfonic acid derivatives. Synthesis and antitumor activity of di- and tetra(benzylsulfonyl)diamines

Selecting these compounds for the synthesis was inspired by data on the antitumor activity of alkanesulfonic acid esters and aliphatic diols, where the maximum efficacy was observed for 1,4-bis(methanesulfonyloxy)butane (myelosan) [3]. The effect of structural features on the antitumor activity was elucidated by replacing oxygen in the sulfonic acid esters by sulfur and nitrogen [4]. Taking into account these data

Synthesis and Antitumor Activity of 2-S-Substituted Pyrimidine Derivatives

A series of new 2-S-substituted pyrimidine derivatives has been synthesized via the interaction of 2-mercaptopyrimidines with various alkylbromides, chloracetamide, and unsubstituted and substituted benzyl chlorides. The synthesized compounds have been tested with respect to antitumor activity.

Synthesis and Antitumor Activity of New Methylglyoxal and Glucosone Bisthiosemicarbazones and Their Copper Complexes

I, II: R = C3H7 (a), i-C3H7 (b), C4H9 (c), CH3 (d), C2H5 (e, g), C4H9 (f); R = CH3 (a – e), (CHOH)3CH2OH (f, g); X = H (a – c, f), NO2 (d), Cl (e, g). The initial substituted thiosemicarbazides were synthesized as described previously [5]. Bisthiosemicarbazones Ia – Ig were obtained using reactions of these compounds with methylglyoxal and glucosone [3]; the products were identified by TLC, elemental analyses, and IR and UV spectroscopy. In the next stage, compounds Ia – Ig interacted with equimolar amounts of copper sulfate to yield the corresponding copper bisthiosemicarbazones IIa – IIg. The products appeared as crystalline substances of red color, soluble in DMSO, DMF, and some other organic solvents. The proposed structures of the synthesized compounds were confirmed by measuring their spectrophotometric characteristics in the visible range, by the data of spectrophotometric titration, and by comparison with the properties of analogous complexes with structures refined using EPR data [1 – 3]. Two bisthiosemicarbazones (Ie, Ig) and their copper complexes (IIe, IIg), containing the same substituents in the benzene ring, were characterized by distribution coefficients (K d ) in the octanol – water system. It was established that the lipophilicity of methylglyoxal bisthiosemicarbazone (Ie) is higher than that of glucosone bisthiosemicarbazone (Ig), while the copper complexes of both bisthiosemicarbazones possess almost equal lipophilicities. It was established that the synthesized methylglyoxal bisthiosemicarbazones and their copper complexes Ib – Id, IIb – IId possess low acute toxicities (LD 10

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 Conversions of Polyhedral Compounds. 32. Synthesis and Antibacterial Activity of Azaadamantane-Containing Azomethine Dihydrochlorides

New azomethines (Schiff bases) containing azaadamantane groups on one side and several biologically active compounds on the other were synthesized. The antibacterial activity of their dihydrochlorides showed that azomethines containing a nitrofuryl group were most active.

Synthesis and Antimicrobial Properties of Ammonium Salts Containing a Substituted Butyn-2-yl Group

Interaction of 1-dimethylamino-4-diethylaminobutyn-2, 1-dimethylamino-4-piperidinobutyn-2, and 1-dimethylamino-4-morpholinobutyn-2 with the corresponding alkyl esters of monobromo(chloro)acetic acid was used to synthesize novel monoammonium salts. Studies of the antimicrobial activity of the resulting compounds showed that salts containing hydrophobic alkoxycarbonylmethyl radicals had marked antibacterial activity against Gram-positive and Gram-negative microorganisms.