Search for substances with antioxidant and antiamnestic activities among 2-substituted 4-(3H)-quinazolones

We have synthesised some of 2-substituted 4-(3H)-quinazolones by the reaction with benzaldehyde and cinnamic aldehyde and their derivatives. It is shown that the intensity of the reaction depends on electrophilic properties of carbonyl compounds and steric factors. The elemental analysis, ultraviolet (UV), infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy confirmed the structure of synthesised compounds, their individuality being checked by thin-layer chromatography. The results of biological experiments show that the synthesised 2-substituted 4-(3H)-quinazolones have an expressed antioxidant and antiamnestic activity and are prospective for further research of their nootropic activity.     

Photolysis of 3-methyl- and 3-phenyl-4-amino-2-methyl-1-phenyl-3-pyrazolin-5-one (author's transl)

Photolysis of 3-Methyl- and 3-Phenyl-4-amino-2-methyl-phenyl-3-pyrazolin-5-one During the irradiation of aqueous solutions of 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one ( 1d ) besides the compounds 2 and 3 characteristic photolysis products of pyrazolones (Type I), the compound 12 is obtained, which was formed from two molecules of 1d . 4-Amino-2-methyl-1,3-diphenyl-3-pyrazolin-5-one, however isomerises to 8, which upon further irradiation fragments into several components two of them being N-phenyloxamide and N,N′-diphenyloxamide.     

Synthesis,analgesic, anti-inflammatory and antibacterial activities of some novel 2-phenyl-3-substituted quinazolin-4(3H) ones

A series of novel 2-phenyl-3-substituted quinazolin-4(3H)-ones have been synthesized by treating methyl-N-(2-phenyl quinazolin-3-yl-4(3H)-one) dithiocarbamate with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. All the test compounds exhibited significant activity, the compounds A1, A2 and A3 shown more potent analgesic activity, and the compound A3 shown more potent anti-inflammatory activity than the reference standard diclofenac sodium.     

Synthesis of 6-substituted 2-phenyl-3-(5-substituted mercapto-1,3,4, thiadiazol-2-yl)quinazolin-4-(3H)-ones as antitubercular agents

2-Amino-5-mercapto-1,3,4-thiadiazole was condensed with various 6-substituted 2-phenylbenzoxazin-4 (3H)-ones to yield the compounds 1 . When these compounds were subjected to mercaptoetherification the title compounds 2–4 were obtained. They were screened for their antitubercular activity against Mycobacterium smegmatis and Mycobacterium tuberculosis H₃₇ Rv in vitro. Structure-activity relationships were established.     

Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-methyl-3-substituted quinazolin-4-(3H)-ones

A series of novel 2-methyl-3-substituted quinazolin-4-(3H)-ones have been synthesized by treating (2-methyl-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid. The compounds synthesized were investigated for analgesic, anti-inflammatory and antibacterial activities. All the test compounds exhibited significant activity, the compounds VA2, VA3 and VA4 shown more potent analgesic activity, and the compounds VA3 and VA4 shown more potent anti-inflammatory activity than the reference compound diclofinac sodium.     

Synthesis of 3-substituted 6-methyl-4-pyridyl-2 (1H) pyridones and testing of their cardiovascular action

Reaction of our previously described and in 4- and 6-, respectively, position with 3- and 4-, respectively, substituted 3-cyan-2(1H)-pyridones 4 and 5 with concentrated sulphuric acid had yielded the 3-carbamoyl-pyridones 8 and 9. Hofmann reaction was followed and the 3-amino substituted pyridones 10 and 11 were formed. As by-products the 5-bromo substituted 3-amino-pyridones 12 and 13 were obtained. 4 and 5 were refluxed in the presence of diluted sulphuric acid to yield the decarboxylated pyridones 14 and 15. Cardiotonic Activity of the compounds 4-9 compared to amrinone (Cordemcura) was investigated.     

Design, synthesis and antihistaminic (H1)activity of some condensed 2-(substituted)arylaminoethylpyrimidin-4(3H)-ones

The synthesis and potential H1 receptor antagonistic activity of two novel series of condensed 2-arylaminoethylpyrimidin-4(3H)-ones (4, 5) and 4-amino-2-arylaminoethyl pyrimidines (6) have been reported. All the novel compounds were found to antagonize histamine in a competitive and reversible manner. When tested on guinea-pig ileum, compounds exhibited H1-antagonistic activity, (pA2 values) in the range of 8.6 to 9.7. Some of the lead compounds were evaluated by an in vivo method and were found to protect the guinea pigs against the histamine induced asphyxic shock at the doses comparable to or lower than those of the standard drugs, cetirizine (CAS 83881-51-0) and terfenadine (CAS 50679-08-8). The pA2 acetylcholine values of some of the lead compounds reflect about 1000-fold selectivity for histamine (H1) receptors. The 4-aminopyrimidines (6) were found to be more selective than their 4-one analogs (4, 5). In the radioligand binding study, one of the lead compounds, 6e, was found to bind reversibly at the histamine H1 receptor with the K1 value of 1.3 mumol/l and IC50 of 3.8 mumol/l. The lead compounds were found to have negligible sedative potential when tested in vivo. An indirect type of molecular modeling approach, using temelastine (CAS 86181-42-2) as the standard ligand, indicates that the potent activity of 4, 5 and 6 may be due to the increased spacer chain length between the pyrimidine nucleus and the side-chain aromatic ring.     

Synthesis of 3-cyano-6-methyl-4-pyridyl-2(1H)-pyridinethiones as well as 2-substituted 6-methyl-4-pyridyl-pyridine-3-carbonitriles and 3-carbonic acid amides, respectively, and testing their cardiovascular activity

By the base catalyzed reaction of our previously described 3-cyano-6-methyl-4-pyridyl-2(1H)-pyridinethiones 1 and 2, respectively, with branched and unbranched, respectively, alkyl, aralkyl-, alkinyl-, hydroxyalkyl-, ethoxycarbonyl- and carbamoylalkylhalides the new in 2-position substituted 6-methyl-4-pyridyl-pyridine-3-carbonitriles 15-30 were formed. By means of oxidation of the 2-methylthio-substituted pyridine-3-carbonitriles 3 and 4 with potassium periodate and potassium permanganate in diluted acetic acid, respectively, the sulfinyl compounds 5 and 6, respectively, and the sulfonyl compounds 7 and 8, respectively, were prepared. By heating of 3 and 4, respectively, with concentrated sulphuric acid the 2-methylthio-pyridine-3-carboxamides 9 and 10 were obtained. The oxidation of these compounds with potassium periodate and potassium permanganate, respectively, had yield the pyridines 11 and 12, respectively, as well as 13 and 14, respectively.     

4-苯基-5-乙氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-酮的绿色合成研究

目的探索操作简便,环境友好的4－苯基－5－乙氧羰基－6－甲基－3,4－二氢嘧啶－2（1H）－酮的合成方法。方法 以苯甲醛、乙酰乙酸乙酯和尿素作为起始原料,在无溶剂和微波加热条件下,选择1－丁基－3－甲基咪唑氯盐和1－丁基－3－甲基咪唑－L－乳酸盐两种不同的离子液体分别催化Biginelli反应制备4－苯基－5－乙氧羰基－6－甲基－3,4－二氢嘧啶－2（1H）－酮,并比较两种离子液体的催化效果。结果两种离子液体在微波、无溶剂条件下均可催化Biginelli反应制得目标化合物,其中1－丁基－3－甲基咪唑－L－乳酸盐作为催化剂目标化合物收率较高。结论以离子液体－丁基－3－甲基眯唑－L－乳酸盐作为催化剂,经微波、无溶剂Biginelli反应制备4－苯基－5－乙氧羰基－6-甲基－3,4－二氢嘧啶－2（1H）－酮,是一种易于操作的绿色合成方法。