L. N. Yakhontov

Synthesis and chemotherapeutic studies of 2-styryl-4-(δ-diethylamino-α-methylbutylamino)quinazolines

The compounds were synthesized by a previously developed general method [7, 8], from the appropriate 2-methyl-4-quinazolones (I), which were converted via the 2-methyl-4-chloroquinazolines (II) into the 2-methyl-4-(~-diethylamino-~-methylbutylamino)quianazolines (III), followed by condensation with substituted aldehydes to give the 2-styryl-4-(~-diethylaminomethylbutylamino)quinazolines (IVa-o) (Table I) required for chemotherapeutic study.

Synthesis and chemotherapeutic investigation of substituted 2-(δ-phenylbutadienyl)-4-aminoquinazolines and some of their 2-styrylquinazoline analogs

Experiments on the condensation of 2-methyl-4-(5-diethylamino-~-methylbutylamino)-7chloroquinazoline (Ib) with acetaldehyde failed to give 2-(~-methylvinyl)-4-(5-diethylaminoa-methylbutylamino)-7-chloroquinoazoline, which could then have been reacted with aromatic aldehydes to give the required product~ On heating equimolar amounts of (Ib), acetaldehyde, and acetic anhydride in sealed glass tubes for 6 h at 150~ approximately 30% of unreacted methylquinazoline (Ib) was recovered, and a difficultly-separable mixture of products of differing degrees of condensation was obtained~ We therefore resorted to synthesizing the required compounds by condensing the methyl derivatives (Ia-c) with the corresponding cinnamaldehydes (IIa-c) the preparation of which from the aromatic aldehydes and acetaldehyde has been described [12-14].

Synthesis and antibradykinin properties of pyridine and triazine analogs of parmidine

The bis-N-methylcarbamic ester of 2,6-bishydroxymethylpyridine is manufactured under the names parmidine, pyridinol carbamate, Anginin, Prodektinj etc., and is used in the treatmen~ of arteries affected by atherosclerosis and diabetes [1-4]. The effectiveness ofparmidine depends no a large extent on its antlbradykinin properties. Depending on the dose and concentration employed, parmidine decreases or completely eliminates the decrease in tonus of the gut and bronchial musculature caused by bradykinin [5], exerts a normalizing effect on the tonus and permeability of microvessels destroyed by the action of endogenic and exogenic kinins [6, 7], acts as an analgesic~ and possesses moderate hypocoagulating properties [8].

Synthesis and anti-inflammatory activity of substituted 2-styryl-4-(δ-diethylamino-α-methylbutylamino)-6-nitro- and 2-styryl-4-(δ-diethylamino-α-methylbutylamino)-6-aminoquinazolines

Reaction of nitroquinazoline I with phosphorus oxychloride in the presence of dimethylaniline formed, by analogy with the reactions of other substituted quinazolones carried out in our earlier work [i], 2-methyl-4-chloro-6-nitroquinazoline (II). Because the 4-chloro atom of compound II is highly labile the substituted 2-methyl-4-amino-6-nitroquinazoline (III) could be prepared in 76% yield by refluxing the chloro derivative II with ~-diethylamino-~-methylbutylamine in benzene. Condensation of the substituted 2-methylquinazo!ine III with various aldehydes under conditions like those described earlier for the synthesis of other styrylquinazolines [4, 5] gave compounds IV. We carried out the selective reduction of the nitro group in position 6 of the quinazoline nucleus of styrylquinazolines IV by two methods -heating with sodium sulfide in aqueous alcohol and reaction with hydrazine hydrate in the presence of a nickel catalyst. Compounds V were formed quite smoothly and selectively in yields of about 60% by the first route. The second method was less selective and required additional purification of the products V.