Reaction of 3-(2,3-epoxypropyl)-4(3H)-quinazolinone and/or its 6,7-dichloro-and 7-bromo--6-chloro derivatives (lb, Ic) with 5-diethylamino-2-pentylamine, 3-diethylaminomethyl-4-hydroxyaniline, 3,4-methylenedioxyaniline and 4-dimethylaminoaniline gave the corresponding substituted 4(3H)-quinazolinones, IIa, IIIb, IVb, Vc and VIc. Reactions of 3-(2-chloroethyl)-4(3H)--quinazolinones with the substituted anilines, pyridine and pyrrolidine gave rise to 3-(2-aminoethyl)-4(3H)-quinazolinones VIIla -VlIIj, IX and X. The piperidine derivative XI was obtained by the action of 1-(2-chloroethyl)piperidine on 4(3H)-quinazolinone. Reactions of 2-chlorobenzyl chloride 4-chlorobenzylchloride and 3,4,5-trimethoxybenzoyl chloride with 4(3H)-quinazolinone afforded 3-(2-chlorobenzyl)-, 3-(4-chlorobenzyl)-4(3H)-quinazolinone and 3-(3,4,5-trimethoxybenzoyl)-4(3H)-quinazolinone (XII, XIII, XIV). All the compounds were screened for coccidiostatic and antihelmintic activity.Since the alkaloid febrifugin is known to have both the coccidiostatic and the antimalaric effects, we have extended our previous study of 4(3H)-equinazolinones 1 by further 3-(2-hydroxypropyl)-4(3H)-quinazolinones, of which three have 5-diethylamino-2-pentylamino or 3-diethylaminomethyl-4-hydroxyanilino grouping in the side chain. These substituents are typical of a number of the synthetic antimalarics. In their preparation we adhered to the method described previousli; the action of l-chloromethyloxirane on 4(3H)-quinazolinone and its 6,7-dihalogeno derivatives gave rise to the corresponding 3-(2,3-epoxypropyl)-4(3H)-quinazolinones I a, Ib and Ie, whose reactions with 5-diethylamino-2-pentylamine and 3-diethylaminomethyl-4-hydroxyaniline afforded the products IIIb, [Vb and VIc. Analogously, the reactions of 3-(2,3-epoxypropyl)-4(3H)-quinazolinone with 4-dimethylaminoaniline, and of 7-bromo-6-chloro-3-(2,3-epoxypropyl)-4(3H)-quinazolinone with 3,4-methylenedioxyaniline gave the compounds IIa and Ve, respectively.Further we investigated the effect of shortening the aliphatic bridge between N(3) of the quinazolinone ring and the nitrogen of the basic side chain or the aromatic ring on the coccidiostatic and antihelmintic efficacy. For this purpose we synthetized compounds of the type 3-(2-anilinoethyl)-4(3H)-quinazolinone, VIIIa -VIIIj, and · analogous compounds with a pyridine, pyrrolidine or piperidine residue as the basic component (IX -XI). With the exception of compound XI their syntheses started from 4(3H)-quinazolinone; its reaction with 2-chloroethanol gave 3-(2-hydro-
2-Phenylbenzimidazoles I-VI with chlorine atom or methoxy group on the benzene ring were prepared by a modified method. Acylation of 2-aminobenzimidazole with substituted benzoyl chlorides afforded the 2-benzamidobenzimidazoles VII-XXXVI. All these compounds were tested for anthelmintic and coccidiostatic activity.
Condemation of aliphatic and aliphatic-aromatic a-diketones, and of substituted benzils with 2,3-and 3,4-diaminobenzoic acids and with 4,5-diamino-2-hydroxybenzoic acid gave 74 5-and 6-quinoxalinecarboxylic acids, with the same or different alkyls and aryls as substituents at positions 2 and 3_ The compounds with different substituents at positions 2 and 3 were resolved into positional isomers. Their structures were determined by means of the dipole moments. The compounds were tested for tuberculostatic activity. Some exhibited it in vitro (LI, L VII), but failed ill riro.A ~igJlificant tuberculostatic activity was demonstrated with some derivatives of quinoxaline and benzo[b Jquinoxaline 1 -3. The in vivo tests also showed a high activity, but their side effects and too firm binding to tissues 3 make them clinically unsuitable. Since the introduction of a carboxyl group into an organic compound u~ ually ,uppresses its affinity to tissues and speeds up its secretion, we have prepared variously substituted 5-and 6-quinoxalinecarboxyIic acids. Some of them have been described before, but were not te5ted bacteriologically.To synthetize them we used the general reaction of ex-diketones with aromatic o-diamines. The latter were 2,3 and 3,4-diaminobenzoic acids and 4,5-diamino--2-hydroxybenzoic acid. These were condensed with aliphatic, cycloaliphatic and aliphatic-aromatic ex-diketones, as well as with variously substituted benzils. These reactions proceeded smoothly and largely gave good yields. In most cases we used to advantage the method of van der Stellt and coworkers 4 , who heated an equimolar mixture of an ex-diketone and an o-diamino compound in acetic acid (method A).However, in using this method we sometimes obtained blackish products. In such ca~.es it proved rewarding to replace acetic acid by ethanol (method B). If the starting cx-diketone was at least partially soluble in water it was possible to use water acidified with hydrochloric acid (method C), as described by Perella and coworkers 5 • In the condensation of non-symmetrical cx-diketones (different R's) mixtures of positional isomers were formed. With only one exception, these were resolved by cry,tallization or column chromatography. However, demonstration of their structures was a problem. First we tried the synthetic method, attempting condensation of l-methyl-2-phenylethanedione with 4-nitro-5-aminosalicyclic acid and/or Collect:cn Czechoslovak Chern.
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