R. S. Sukasyan

Synthesis and biological properties of 3-phenyl-and 3-phenethyl-5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines

The interaction of 3-methyl-3-ethyl-1-amino-2-ethoxycarbonyl-3,4-dihydronaphthaline with phenyl-and phenethylisothiocyanates and subsequent treatment of the reaction mix with alkali led to the formation of the corresponding 3-phenyl-and 3-phenethyl-5-methyl-5-ethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazolines (II, III). Condensation of the resulting 2-thioxobenzo[h]quinazolines II and III with halogenides of different structures was used to synthesize 2-sulfanyl-substituted 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (IV–XXVII). Reaction of benzo[h]quinazoline II with 2-ethanolamine and 3-propanolamine yielded 5-methyl-5-ethyl-3-phenyl-2-(β-hydroxyethylamino)-and 5-methyl-5-ethyl-3-phenyl-2-(γ-hydroxypropylamino)-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (XXVIII, XXIX) respectively. The effects of the resulting compounds on brain monoamine oxidase (MAO) activity were studied in in vitro experiments. Most of the compounds were found to inhibit 5-HT deamination. The antitumor activities of these compounds were studied using two models of grafted mouse tumors — Ehrlich ascites carcinoma (EAC) and sarcoma 180. Some of the study compounds had moderate therapeutic effects (suppressing tumor growth by 50–60%, p < 0.05).

Synthesis, antitumor, and anti-monoamine oxidase properties of 2,4,4-trisubstituted triazolobenzo[ h ]quinazolines

The interaction of 1-amino-3-methyl-3-ethyl-3,4-dihydronaphthaline-2-carbonitrile (I) with propanoic acid chloranhyride was used to synthesize the corresponding amidonitrile II, which was then cyclized to form 2,5-diethyl-5-methyl-4-oxo-5,6-dihydrobenzo[h]quinazolin-4(3H)-one (III). Interaction of aminonitrile I with triethylorthoformate and carboxylic acid hydrazides yielded 2-substituted 4-methyl-4-ethyl-4,5-dihydrobenzo[h][1, 2, 4] triazolo[1,5-c]quinazolines (IV-XVIII). The antitumor and anti-monoamine oxidase properties of the compounds obtained were studied.

Synthesis and biological activity of 5-methyl-5-ethyl-4-oxobenzo[h]quinazolines

Abstract9-Methyl-9-ethyl-8-oxo-2,3,4,5,6,7,9,10-octahydrobenzo[h]azepino[2,l-b]quinazoline was obtained via the interaction between 1-amino-3-methyl-3-ethyl-2-ethoxycarbonyl-3,4-dihydronaphthalene (aminoester) and caprolactam in the presence of phosphorus oxychloride. 5-Methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazoline was synthesized using the reaction of aminoester with formamide under the conditions of the Niementowski reaction. This aminoester reacts with benzoyl isothiocyanate at room temperature with the formation of an N′-benzoylthioureido derivative, which exhibits cyclization in the presence of an alkali, yielding 5-methyl-5-ethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazoline. The latter is converted into 2-substituted 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines by reactions with alkyl-, allyl-, benzyl-and metalylhalogenides, 2-bromoethanol, chloroacetic acid ester, and amides of halogen-substituted acetic acids. The effect of the synthesized compounds on monoamine oxidase (MAO) activity in vitro, and the antitumor properties of some compounds in vivo were evaluated. It is established that most compounds exhibit significant antitumor and anti-MAO activity.

Antimonoamineoxidase and antitumor activity of 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines

Reactions of 3-methyl-3-ethyl-1-amino-2-cyano-3,4-dihydronaphthalene (I) with carboxylic acid chlorides lead to the formation of either monoacylated (II–VII) or diacylated (VIII–X) products depending on the amount of reactants. When dry hydrogen chloride is bubbled through alcohol solutions of the amides (II–VII), these compounds cyclize to 2-substituted 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (XI–XVI). Alkylation of benzo[h]quinazolines XI and XII yielded 3-substituted benzo[h]quinazolines (XVII–XIX). Antitumor and antimonoamineoxidase properties of the synthesized compounds have been studied. Experiments in vitro have shown that some of these compounds exhibit antimonoamineoxidase activity. Compounds II and IV showed weak inhibition of Ehrlich’s ascites carcinoma (by 30 and 47%, respectively) at doses of 100–250 mg/kg in chemotherapeutic experiments.

Synthesis and neurotropic properties of 1-amino-2-substituted 8,9-dihydro-6h-pyrano(thiopyrano)[4,3-d]-thieno-[2,3-b]pyridines and- thieno[2,3-c]-2,7-naphthyridines

Thieno[2,3-b]pyfidines are widely used both as reagents for the synthesis of complex condensed heterocyclic systems [1 -3 ] and as pharmacologically active compounds [4, 5]. This class includes substances producing an anticonvulsive effect and possessing affinity with respect to benzodiazepine receptors [6, 7]. The purpose of this work was to synthesize l-amino-2substituted 8,9-dihydro-6H-pyrano(thiopyrano)[4,3-d]-thieno[2,3-b]pyridines and -thieno[2,3-c]-2,7-naphthyridines ( X XXI) and study their neurotropic properties.

Synthesis and Biological Activity of New 3-Ethyl-2-Thioxo-2,3-Dihydro-1H-Spiro[Benzo[h]-Quinazolin-5,1′-Cyclohexane]-4(6H)-One Derivatives

2-Sulfanyl-substituted 3-ethyl-3H-spiro[benzo[h]quinazolin-5,1′-cyclohexane]-4(6H)-ones were synthesized by reacting 3-ethyl-2-thioxo-2,3-dihydro-1H-spiro[benzo[h]quinazolin-5,1′-cyclohexane]-4(6H)-one with halides. 2-Hydrazino-3-ethyl-3H-spiro[benzo[h]quinazolin-5,1′-cyclohexane]-4(6H)-one was prepared from 3-ethyl-2-methylthio-3H-spiro[benzo[h]quinazolin-5,1′-cyclohexane]-4(6H)-one and transformed into 1-sulfanyl-substituted triazolobenzoquinazolines. Several of the synthesized compounds exhibited high anti-monoamine oxidase and antitumor activity.

Synthesis and antimonoamineoxidase activity of 4-methoxybenzylguanidine and its sulfate

4-Methoxybenzylguanidine and its sulfate were patented as monoamine oxidase (MAO) inhibitors [1]. However, our attempts to develop efficient synthetic pathways revealed that the physicochemical characteristics available in the literature concerning the structure of these compounds differ from our data and are mutually contradictory. For example, the original work of Saigo [2] reported m.p. =210-212~ for 4methoxybenzylguanidine sulfate, while the later work [3] indicated 2 1 5 216~ [3]. When we reproduced the reaction pathway from [3] (scheme 1), it was found that the product I with m.p. = 215-216~ (I) is not an individual compound but represents a mixture of two guanidine derivatives with m.p. =210-212~ (Ia) and 234-235~ (Ib). It was suggested that the stage ofanisole chloromethylation involved in scheme 1 leads to the formation of an admixture of 2methoxybenzyl chloride besides the main product, 4methoxybenzyl chloride. As a result, the final product also comprises a mixture of two isomers, 2and 4-methoxybenzylguanidine sulfates. Scheme 1

Synthesis and biological activities of some amides of 2-oxo-1-oxapyro[4,5]decane-4-carboxylic acids

negatively affects the condition of the intrauterine fetus. Apparently, to judge from their chemical structures, the compounds that we have studied possess a double mechanism of action, ganglioblocking and beta-adrenoblocking. However, their beta-adrenoblocking properties are less pronounced than with anapriline; when they are administered intravenously, the arterial pressure is not lowered and there is only a temporary reaction on the injection, which lasts 30-60 sec, after which the arterial pressure is restored to the initial value; in that case the frequency of heart contractions does not change substantially.