B. T. Garibdzhanyan

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.

Synthesis and antitumor activity of pyrano[4′,3′:4,5]pyrido[2,3-b]thieno[3,2-d]-1,2,3-triazine and l,2,3-triazino[4′,5′:4,5¦thieno-[2,3-c]isoquinoline derivatives

Methods for the synthesis of new heterosystems of condensed thieno[3,2-d]-1,2,3-triazines on the basis of pyrido[2,3-b]thiophenes have been developed. The antitumor activity of the synthesized compounds was studied and several compounds possessing low toxicity and moderate antitumor activity were found.

Synthesis and antitumor activity of 3,4,5-substituted 1,2,4-triazoles

Conditions for effective alkylation of new 3,4-substituted-5-mercapto-1,2,4-triazoles with various alkylating agents are established. Several compounds possessing pronounced antitumor activity have been found in experiments using two xenograft tumor models.

Imidazole Derivatives. XXX. Synthesis and Antitumor Activity of 4-amyloxy-3-nitroacetophenone 2-imidazolinyl-2-hydrazone and Related Compounds

The antitumor properties of 2-imidazolinyl-2-hydrazones of acetophenones with various substituents in the benzene ring have been studied. High activity is found for 4-amyloxy-3-nitroacetophenone 2-imidazolinyl-2-hydrazone, which points to the expediency of its further investigation.

Antitumor activity of substituted methylglyoxal bisthiosemicarbazones and their copper(II) chelates

A series of new bisthiosemicarbazones of methylglyoxal and their copper(II) complexes were synthesized. Evidence of antitumor properties of some products combined with low toxicity shows that further searching for antitumor agents in this group of compounds may be promising.

Synthesis and antitumor properties of 1,3-diaza-2-phosphaadamantane derivatives, phosphoryl-containing 3,7-diazabicyclo[3.3.1]nonane, and 1,3-diazaajdamantane

In the search for new antitumor compounds, we synthesized a number of 3,7-diazabicyclo[3.3.1]nonanes and 1,3diazaadamantanes containing a phosphoryl group, and compounds derived from the previously unknown 1,3-diaza-2phosphaadamantane. We used phenoxyand bis(2-chloroethyl)amino groups as substituents in the phosphoryl group. 1,5-Dimethyl-9-oxo-3,7-diazabicyclo[3.3.1 ]nonane (I) [ 1 ] and 5,7-dimethyl-6-oxo-l,3-diazaadamantanes ( V a d ) [2] were used as starting compounds; some of their derivatives exhibited antitumor activity in the experiments [3, 4]. 3-Phosphoryl-substituted 3,7-diazabicyclo[3.3.1]nonanes (IIa, b) were synthesized in the reaction of diazabicyclononane I with diphenyl phosphorochloridate and phenylbis(2-chloroethyl)-phosphoramidochloridate [5] (in the ratio 1 : 1). The excess of diphenoxyphosphoryl chloride (1:2) did not lead to the formation of the corresponding 3,7-disubstituted derivative of 3,7-diazabicyclononane, although we showed that diazabicyclononane IIa readily reacted with propyl isothiocyanate to form the mixed 3,7-disubstituted derivative of 3,7-diazabicyclononane (III). The interaction of 1,3-diazaadamantanes containing unsubstituted (Va), Cmono(Vc), and the C,C-disubstituted (Vb) methylenediamine group with diphenoxyphosphoryl chloride also leads to diazabicyclononane IIa. 2-Phenyl-l,3-diazaadamantane derivatives with a substituted phosphoryl group on the benzene ring (IVa, b) were synthesized by condensation of diazabicyclononane I with 4-formylphenyl diphenyl phosphate or phenyl-bis(2-chloroethyl)phosphoramidate [the last-mentioned compounds were obtained from sodium 4-formylphenolate and diphenoxyphos-

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 biological activity of pyrano[4,3-d]furo[2,3-b]pyridine derivatives

Furopyridines have a wide spectrum of biological activity [1 3] and some of them are used in medicine [4], thus stimulating a search for biologically active compounds among the derivatives of a new heterocyclic system, pyrano[4,3d]furo[2,3-b]pyridine. Synthesis was performed on the basis of 3-phenacyloxy-4-cyanopyrano[3,4-c]pyridines ( I a u) obtained earlier [5]. The presence of an active methylene group in these compounds makes it possible to carry out intramolecular cyclization in the presence of sodium ethylate, which yields 9-aminopyrano[4,3-d]furo[2,3-b]pyridines ( I I a u).

Synthesis and biological activity of condensed derivatives of thieno[3,2-d]thiazolo(thiazino, thiazepino)[3,2-a]pyrimidines

Methods for the synthesis of new heterosystems including condensed pyrano[4′,3′:4,5]pyrido[2,3-b]-thieno[3,2-d]thiazolo(thiazino, thiazepino)[3,2-a]pyrimidines, thiazolo(thiazino, thiazepino)[3″,2″:1′,2′]pyrimido[4′,5′:4,5]thieno[2,3-c]isoquinolines, and cyclopenta[4′,3′:4,5]pyrido[2,3-b]thieno[3,2-d]thiazolo(thiazino)[3,2-a]pyrimidines are developed. The synthesis is carried out on the basis of 1-amino-2-ethoxycarbonylpyrano[4,3-d]thieno[2,3-b]pyridines and -thieno[2,3-b]isoquinolines. Antitumor and anticonvulsant properties of the synthesized products have been evaluated. Compounds possessing low toxicity and moderate biological activity are found.

Synthesis and biological properties of 5,5-diethyl-2-substituted 4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazoline derivatives

A series of new derivatives of benzo[h]quinazolines containing diethyl substituents at position 5 were synthesized. The alkylation of some 2-substituted 5,5-diethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines with methyl iodide led to N-substituted products, while a similar reaction with ethyl iodide led to a mixture of N-substituted and O-substituted products. Some of the synthesized 5,5-diethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines exhibit pronounced antiaminooxidase and weak antitumor properties.