M. I. Vakhrin

Synthesis and antimicrobial activity of 1-(4-hydroxyphenyl)-4-acyl-5-aryl-3-hydroxy-3-pyrrolin-2-ones

The reaction of methyl esters of acylpyruvic acids, 4-aminophenols, and aromatic aldehydes leads to the formation of 1-(4-hydroxyphenyl)-4-acyl-5-aryl-3-hydroxy-3-pyrrolin-2-ones. The proposed structures of the synthesized compounds were confirmed by IR and PMR spectroscopy. The antibacterial activity of some of the newly synthesized compounds was studied.

Substituted Amides and Hydrazides of Dicarboxylic Acids. Part 14. Synthesis and Antimicrobial and Antiinflammatory Activity of 4-Antipyrylamides, 2-Thiazolylamides, and 1-Triazolylamides of Some Dicarboxylic Acids

In continuation of our search for new biologically active substances among substituted amides of dicarboxylic acids [1], we have synthesized a series of 4-antipyrylamides, 2-thiazolylamides, and 1-triazolylamides of succinic (Ia – Ic), maleic (IIa – IIc), citraconic (IIIa – IIIc), and phthalic (IVa – IVc) acids. Compounds I – IV were obtained by acylating the corresponding dicarboxylic acid heterylamides with succinic, maleic, citraconic, or phthalic anhydrides under mild conditions using the well-known procedure described previously [2]. The proposed structures of the synthesized compounds were confirmed by the results of spectroscopic measurements (Table 1).

Acylation reaction of the 3,3-dimethylisoquinoline series enaminonitrile and properties of 5,5-dimethyl- 2,3-dioxo-2,3,5,6-tetrahydropyrrolo[2,1-a]isoquinoline- 1-carbonitrile

2-(3,3-Dimethyl-3,4-dihydro-2H-isoquinolin-1-ylidene)acetonitrile containing an enamine fragment has been acylated using acetyl or benzoyl chlorides to give the corresponding enamino ketones. The acylation using oxalyl chloride gives 5,5-dimethyl-2,3-dioxo-2,3,5,6-tetrahydropyrrolo[2,1-a]-isoquinoline-1-carbonitrile. Reaction of the latter with guanidine carbonate or o-phenylenediamine is accompanied by opening of the pyrrole ring and heterocyclization to give the corresponding 2-amino-4-imidazolone and 2-quinoxalone derivatives. Linear amines were formed in similar reactions with m-toluidine, 1-aminoadamantane, o-aminophenol, and 2-amino-3-hydroxypyridine.

Synthesis of enaminoamides of the 1,2,3,4-tetrahydroisoquinoline series

Enaminoamides of the 1,2,3,4-tetrahydroisoquinoline series having the Z-configuration were synthesized by the reaction of dialkylbenzylcarbinols cyanaceamides.

Synthesis of 2-(3,3-dimethyl-3,4-dihydroisoquinol-1-yl)propanoic acid amides and their influence on blood coagulation

A series of new 2-(3,3-dimethyl-3,4-dihydroisoquinol-1-yl)propanoic acid amides have been synthesized using the reaction of methyliodide with 2-(3,3-dimethyl-1,2,3,4-tetrahydroisoquinolin-1-idene)ethanamides that proceeds on the β-atom of the enamine fragment to form iodides of 2-(isoquinol-1-yl)propanoic acid derivatives. Investigation of the influence of the synthesized compounds on blood coagulation showed that all of them are hemostatics. The most active compounds possess radicals such as morpholine and 2-(3,4-dimethoxyphenyl)ethylamine, are not substituted at the amide fragment, and decrease the blood coagulation time by 14–16%.

Synthesis of 1-aroylmethyl-and 1-aryloxymethyl-3,4-dihydroisoquinolines and their effects on blood clotting

Acylation of a number of tertiary enamines with aroylchlorides was used to synthesize 1-aroylmethyl-3,4-dihydroisoquinolines. Reaction of 1-chloromethyl-3,3-dimethyl-3,4-dihydroisoquinoline with phenols with interphase catalysis was also used to make 1-aryloxymethyl-3,4-dihydroisoquinoline derivatives. 1-Aroylmethylisoquinolines characteristically had a hemostatic effect, while 1-aryloxymethyl-3,4-dihydroisoquinolines had an anticoagulant effect. The most active compound increased blood clotting by 17.7%.

Enamines of the 1,2,3,4-tetrahydroiso-quinoline series in the Chichibabin synthesis of pyrrolo[2,1-a]isoquinolines and in reaction with oxalyl chloride

It has been shown that the Chichibabin reaction of enamines of the 1,2,3,4-tetrahydroisoquinoline series and 1,2,3,4-tetrahydrobenzo[f]isoquinoline series with p-bromophenacyl bromide leads to pyrrolo[2,1-a]isoquinoline derivatives. The same heterocyclic system is obtained on interaction of 1-alkyl-3,4-dihydroisoquinolines or their benzo[f]-analogs with oxalyl chloride. The obtained dioxopyrrolines form derivatives of benzo[g]quinoxalino[2,3-b]indolizine on condensation with o-phenylenediamine.

Synthesis and tautomerism of 1-substituted 3,3-dialkyl-3,4-dihydroisoquinolines

A number of ethyl esters of 3,3-dialkyl-3,4-dihydroisoquinoline-Δ1(2H), α-α- alkylacetic acids have been synthesized. The effect of replacement of α-hydrogen by alkyl radicals on the azomethine-enamine tautomeric equilibrium was shown.

Chloromethyl and Aryloxymethyl 3,4-Dihydroisoquinoline Derivatives: Synthesis and Study of Antiaggregant and Antihypoxant Properties

Previously we studied a series of isoquinoline derivatives exhibiting antiaggregant effect with respect to thrombocytes [1 – 5] and possessing hypotensive properties [6 – 8]. At the same time, derivatives of 1-chloromethylisoquinoline [9 – 11] are still not characterized with respect to pharmacological activity. To our knowledge, the properties of 1-methylisoquinoline esters were also never reported in the literature. When the ester residue represents an aromatic or benzyl fragment, such molecules differ from papaverine by the presence of an oxygen bridge. In this context, it was of interest to compare the pharmacological properties of these esters and papaverine. The aim of our study was to determine the effect of 1-chloromethyl-3,4-dihydroisoquinolines (II) and benzo[f]isoquinoline esters (IV) on the thrombocyte aggregation and arterial pressure in experimental animals. The latter compounds were selected as objects for the investigation because previously we observed a pronounced hypotensive activity in benzo[f]isoquinoline derivatives [7, 8]. The series of chloromethylisoquinolines IIa – IIe was synthesized by means of the interaction of carbinols Ia – Ie with chloroacetonitrile under the Ritter cyclocondensation conditions [1 – 3, 7, 8]. Esters IVa – IVf were obtained via reactions of compound III, obtained previously by the same method [7], with alcohols and phenols under conditions of phase-transfer catalysis [12]. In particular, the interaction of III with benzyl alcohol to yield compound IVa (R = PhCH2) [12] proceeds in a KOH/benzene system and is catalyzed by 18-crown-6. The interaction between III and phenols, proceeding in a 50 % NaOH/CH2Cl2 system and catalyzed by tetrabutylammonium hydrosulfate, led to phenyl esters IVb – IVf. Data on the yields, structures (R–R), and properties of the synthesized compound are presented in Tables 1 – 3.

Properties of 4-Chloromethyl-2,2-dimethyl-1,2-dihydrobenzo[f]isoquinoline

We have shown that 2,2-dimethyl-4-chloromethyl-1,2-dihydrobenzo[f]isoquinoline, which displays the properties of an enamine, reacts with oxalyl chloride with annelation of the dioxopyrroline ring. At the same time, this compound reacts with S-, O-, and CN-nucleophiles.