共查询到20条相似文献,搜索用时 15 毫秒
1.
Yuriy M. Kononevich Ludmila S. Bobkova Alexander S. Smolski Anatoly M. Demchenko 《Scientia pharmaceutica》2015,83(1):41-48
New 7-thio derivatives of 6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione have been synthesized by the reaction of 3-cyclohexyl-7-thio-6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione with alkylhalogenides. The synthesized compounds were tested for antioxidant activity on the model of Fe2+-dependent oxidation of adrenaline in vitro. It was found that the antiradical activity of 7-thio derivatives of 6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione significantly depends on the structure of the substituent which is part of the thioether fragment of the base molecule. 相似文献
2.
Ozair Alam Suroor A. Khan Nadeem Siddiqui Waquar Ahsan 《Medicinal chemistry research》2010,19(9):1245-1258
A new series of thiazolo [3,2-a] pyrimidine derivatives was designed and synthesized using 4-fluoroaniline and ethylacetoacetate
as starting material. Anti-inflammatory activity was assessed by the rat paw edema method and antinociceptive activity was
evaluated by thermal stimulus technique. The compounds 5-(4-chlorophenyl)-2-(4-fluorobenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid (4-fluorophenyl)amide (3l) and 2-(4-chlorobenzylidene)-5-(4-fluorophenyl)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid (4-fluorophenyl)amide (3q) were found to possess significant anti-inflammatory and antinociceptive activities. These compounds also showed lower ulcerogenic
activity and higher ALD50 values. Compounds with an aryl ring substituted with a smaller electron withdrawing group at the fourth position displayed
better activity than the other derivatives. 相似文献
3.
Polycyclic Azines, XL: Synthesis of Heterocyclic Immunomodulators, II: 3-Mercaptoalkylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones: Synthesis and Test for Immuno-stimulating Activity A series of 3-mercaptoalkylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones 3 was prepared and their immuno-stimulating activity was examined. The title compounds were obtained conveniently by hydrolytic ring cleavage of fused thiazolo- or 1,3-thiazino-thicnopyrimidines 1 under alkaline or acidic reaction conditions. The ms fragmentation of the thieno[2,3-d]pyrimidine-2,4-diones 3 is discussed. In the delayed type hypersensitivity (DTH) test some compounds 3 showed immuno-stimulating activities in the range of isoprinosine. 相似文献
4.
R. Hasegawa T. Kato M. Hirose S. Takahashi T. Shirai N. Ito 《Food and chemical toxicology》1996,34(11-12)
Effects of simultaneous administration of five or 10 heterocyclic amines (HCAs) at low dose levels on rat liver carcinogenesis were investigated using a medium-term bioassay protocol. Male F344 rats were initially given diethylnitrosamine (DEN, 200 mg/kg, ip) and received HCAs starting 2 wk later for 6 wk. All animals were subjected to two-thirds partial hepatectomy at wk 3 and were killed at wk 8. Five carcinogenic HCAs in the first two experiments: 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, 2-aminodipyrido[1,2-a:3′,2′-d]imidazole, 2-amino-3-methylimidazo-[4,5-f]quinoline, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline in experiment 1 and 3-amino-1-methyl-5H-pyrido[4,3-b]indole, 2-amino-6-methyl-dipyrido[1,2-a:3′,2′-d]imidazole,2-amino-3-methyl-9H-pyrido-[2,3-b]indole, 2-amino-9H-pyrido[2,3-b]indole, and 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine in experiment 2] were administered together or individually in the diet at levels of 1/1, 1/5 or 1/25 carcinogenic doses, and all 10 chemicals were given at 1/10 or 1/100 levels in experiment 3. Induction of preneoplastic glutathione S-transferase placental form (GST-P) positive foci was increased in some combination groups over the sums of effects for the individual groups at the same doses (apparent synergism). This was most obvious in the group given all 10 chemicals at the 1/10 dose levels. However, it was of interest that the values in the combined groups were generally very close to the averages of five or 10 individual results for the corresponding higher dose groups, indicating isoadditivity of HCA effects. True (strict) synergism, however, was expected for the results of groups including Ph1P and Trp-P-2 in combination, since they are non-hepatocarcinogenic but induce the key metabolic enzyme for HCAs (CYPIA2). 相似文献
5.
Nimesh R. Kamdar Dhaval D. Haveliwala Prashant T. Mistry Saurabh K. Patel 《Medicinal chemistry research》2011,20(7):854-864
Novel 5-phenyl-1,5-dihydro-2H-chromeno[2,3-d]pyrimidine-2,4(3H)-dithiones, 5-phenyl-3,5-dihydro-4H-chromeno[2,3-d]pyrimidin-4-ones, 7-phenyl-7,9-dihydro-8H pyrimido[5′,4′:5,6]pyrano[3,2-h]quinolin-8-ones, and 4-amino-5-phenyl-1,5-dihydro-2H-chromeno[2,3-d]pyrimidine-2-thiones were synthesized form 2-amino-4-phenyl-4H-chromene-3-carbonitrile. The newly synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, Mass spectra, and Elemental analysis. The compounds were evaluated for their in vitro antitubercular activity against
Mycobacterium tuberculosis H
37
Rv and antibacterial activity against Staphylococcus Aureus [ATCC-25923] and Streptococcus pyogenes [MTCC-443] as Gram-positive, Escherichia coli [ATCC-25922], and Pseudomonas aeruginosa [MTCC-441] as Gram-negative bacterial strains and antifungal activity against Aspergillus
niger [MTCC-282]. Some of these derivatives exhibited pronounced antitubercular and antimicrobial activities. 相似文献
6.
Luo Yilin Ren Yun-Feng Chou Ting-Chao Chen Allan Y. Yu Chiang Liu Leroy F. Cheng C. C. 《Pharmaceutical research》1993,10(6):918-923
A number of isoindolo[l ,2-b]quinazolines and some benzo[4,5]isoquinolino[l,2-b]quinazolines as structural modification analogues of the antitumor compound batracylin were synthesized and evaluated against HL-60 cell growth and in topoisomerase II-mediated DNA cleavage assays. Of the compounds studied, 10,12-dihydro-7,8-methy lenedioxyisoindolo[ 1,2-b] quinazolin-12(10H)-one (1d), 2-amino-10,12-dihydroisoindolo[l ,2-b]quinazolin- 12(10H)-one (1p), and 2-amino-7,8-methylenedioxy-10,12-dihydroisoindolo[l ,2-b]quinazolin-12(10H)-one (1ab) exhibited good inhibitory activities against HL-60 cell lines as well as induction of topo II-mediated DNA cleavage activities. 相似文献
7.
Alaa A. El-Tombary 《Scientia pharmaceutica》2013,81(2):393-422
In the present investigation, some new pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives (7–12) as well as fused pyrazolo[3′,4′:4,5]pyrimido[1,2-b]pyridazin-4(1H)-one (14–16) and 7,8,9,10-tetrahydropyrazolo[3′,4′:4,5]pyrimido[1,2-b]-cinnolin-4(1H)-one (17) ring systems were synthesized using the starting compound 5-amino-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (5). The structures of the newly synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis. The theoretical calculation of their lipophilicity as C log P was performed. The anti-inflammatory activity of all newly synthesized compounds was evaluated using the carrageenan-induced paw edema test in rats using indomethacin as the reference drug. Ulcer indices for the most active compounds were calculated. Seven compounds (10b, 11a–f) showed consistently good anti-inflammatory activity. In particular, 5-{[4-(4-bromophenyl)-3-(4-chlorophenyl)-1,3-thiazol-2(3H)-ylidene]amino}-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (11e) and its 3,4-bis(4-chlorophenyl) analog (11f) were found to be the most effective among the other derivatives, showing activity comparable to that of indomethacin with minimal ulcerogenic effects. Correlation of the biological data of the active compounds with their theoretically calculated C log P values revealed that lipophilicity influences the biological response. 相似文献
8.
A series of new 2-methyl-3-(2-piperazin-1-yl-ethyl)-pyrido[1,2-a]pyrimidin-4-one derivatives 6a-j were synthesized by a nucleophilic substitution reaction of 2-methyl-3-(2-piperazin-1-ylethyl)-pyrido[1,2-a]pyrimidin-4-one
with various sulfonyl chlorides. The compounds were characterized by different spectral studies. All the compounds were evaluated
for their antiproliferative effect using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method
against four human cancer cell lines (K562, Colo-205, MDA-MB 231, IMR-32) for the time period of 24 h. Among the series, compounds
6d, 6e and 6i showed good activity on all cell lines except K562, whereas the other compounds in the series exhibited moderate activity.
Compound 6d could be a potential anticancer agent and therefore deserves further research. 相似文献
9.
N. P. Grigoryan L. A. Tarzyan A. I. Markosyan R. G. Paronikyan R. S. Sukasyan 《Pharmaceutical Chemistry Journal》2011,45(2):79-83
Ethyl 2-cyano-3-cyclohexyl-3-methyl-4-phenylbutanoate was synthesized from ethyl (2Z)-2-cyano-3cyclohexylbut-2-enoate using a Grignard reagent. It was shown that the reaction occurred exclusively at the ethylene
bond. Because this cyanoester contained two asymmetric centers, PMR spectra showed two diastereoisomeric forms. These were
cyclized in the presence of conc. H2SO4 into ethyl 4-amino-2-cyclohexyl-2-methyl-1,2-dihydronaphthalenecarboxylate, which was used to synthesize benzo[h]quinazolines, alkyl-substituted benzo[h]quinazolines, triazole, and tetrazole. 相似文献
10.
Detlef Geffken Raafat Soliman Farid S. G. Soliman Magdi M. Abdel-Khalek Doaa A. E. Issa 《Medicinal chemistry research》2011,20(4):408-420
Two series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4-ones were designed, synthesised, and evaluated
for their antibacterial activities and CDKs inhibitory activities. The pyridazine derivative: 6-phenyl-5-phenylhydrazono-2,3,4,5-tetrahydropyridazine-3,4-dione
(3a) revealed activity against Staphylococcus aureus as Gram-positive bacteria while compound 2-(2-Ethoxyphenyl-5-Phenylpiperazinosulfonamido)-3H-pyrido[2,3-d]pyrimidin-4-one (13c) was showing moderate antifungal activity against Candida albicans. 相似文献
11.
Abstract
A series of 6-substituted 2-[(4-methylene-5-oxo-2-(4-substituted phenyl) tetrahydrofuran-2-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-diones (5, 6) and 2,4-bis[(4-methylene-5-oxo-2-(4-substituted phenyl) tetrahydrofuran-2-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-diones (9, 10) were designed, synthesized, and evaluated for antibacterial activity against Gram-positive and Gram-negative microorganisms. The synthesis of these compounds involved the Reformatsky-type reaction between ethyl α-(bromomethyl)acrylate and the proper ketones. Among these compounds, 2-[(4-methylene-5-oxo-2-phenyl tetrahydrofuran-2-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-dione (5a) is the most active compound and shown the selective inhibition activity against Proteus vulgaris. 相似文献12.
《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(7):545-548
1. Glutathione (GSH) transferase-mediated and non-enzymatic activation and detoxication of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2) were studied in vitro. N-OH-Trp-P-2 is an active metabolite of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), a mutagenic and carcinogenic heterocyclic amine.2. The enzymatic GSH conjugation with N-OH-Trp-P-2 was catalysed by rat-liver GSH transferase and a rat-liver cytosol fraction to form three conjugates (CH-1, CH-2 and CH-3).3. The mutagenicities of the GSH conjugates were studied by using Salmonella typhimurium TA98 as the tester strain.4. The GSH conjugates except for CH-3 were completely detoxicated products, but CH-3 was found to be a more potent mutagen than N-OH-Trp-P-2.5. The mutagenicity of CH-3 seemed to be due to the direct action of the conjugate, but not to N-OH-Trp-P-2 formed from it. 相似文献
13.
Since kainate evokes large non-desensitizing currents at α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, kainate is of limited use in discriminating between AMPA and kainate receptors. Following recent reports that (2S,4R)-4-methylglutamate is a kainate receptor-selective agonist, we have radiolabelled and subsequently characterized the binding of [3H]-(2S,4R)-4-methylglutamate to rabbit whole-brain membranes. [3H]-(2S,4R)-4-methylglutamate binding was rapid, reversible and labelled two sites (KD1 = 3.67 ± 0.50 nM/Bmax1 = 0.54 ± 0.03 pmol/mg protein and KD2 = 281.66 ± 12.33 nM/ Bmax2 = 1.77 ± 0.09 pmol/mg protein). [3H]-(2S,4R)-4-methylglutamate binding was displaced by several non-NMDA receptor ligands: domoate > kainate
-quisqualate
-glutamate > 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) (S)-AMPA = (S)-5-fluorowillardiine > NMDA. Neither the metabotropic glutamate receptor agonists (1S,3R)-ACPD or
-AP4, together with the
-glutamate uptake inhibitor
-trans-2,4-PDC, influenced binding when tested at 100 μM. We conclude that [3H]-(2S,4R)-4-methylglutamate is a useful radioligand for labelling kainate receptors. It possesses high selectivity, and possesses a pharmacology similar to that for rat cloned low-affinity (Glu5 and 6) kainate receptor subunits. 相似文献
14.
A number of new [(4-methyl-2-oxo-2H-chromen-7-yl)amino]methylcoumarins (5a–c), benzofuran (6), and benzoxazol (7) were synthesized through the reaction of 7-amino-4-methylcoumarin (1) with a number of organic halides. In addition, series of N-substituted 2-[(4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetohydrazide (11a–h) and (12a–d) were prepared from the reaction of 2-[(4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetohydrazide (8) with corresponding heteroaryl/alkyl halides (2–4, 9, and 10). The synthesized compounds were characterized by elemental analysis and by spectroscopic techniques such as 1H-NMR, 13C-NMR, and mass spectrometry and were tested for their in vitro antimicrobial activity. The newly synthesized compounds exerted
significant inhibitory activity against the growth of tested bacterial strains and a few of them are found to be potent antimicrobial
agents. 相似文献
15.
Structure of a novel sulphur-containing metabolite of Acluracil (1-allyl-3,5-diethyl-6-chlorouracil)
《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(8):495-498
1. A new sulphur-containing metabolite of 1-allyl-3,5-diethyl-6-chlorouracil, identified as 6,8-diethyl-2-hydroxymethyltetrahydrothiazolo[3,2-c]pyrimidine-5,7 (4H,6H)-dione, has been demonstrated in rabbit urine.2. The mechanism of the formation of this metabolite is discussed and a metabolic pathway for the formation of methylthio metabolites is proposed. 相似文献
16.
Mahesh Chhabria Ishwarsinh Rathod Khushbu Vala Paulomi Patel 《Medicinal chemistry research》2011,20(9):1450-1454
Pyrimidines, either mononuclear or condensed with other heterocycles have established its importance in medicinal chemistry.
Variety of biological activities have been reported by thiazolo[4,5-d]pyrimidine derivatives. The present work describes the synthesis and antifungal activity of several 3-(substituted)-5-(substituted)phenylamino-6-(substituted)phenylthiazolo[4,5-d]pyrimidine-7(6H)-one-2(3H)-thiones. The target compounds were synthesized by cyclocondensation of 4-amino-5-carbethoxy-3-(substituted)thiazolo-2(3H)-thione and S-methyl di(substituted)phenylisothiourea. All synthesized compounds were tested for minimum inhibitory concentration against
different fungal strains such as, Aspergillus niger, A. clavatus and Candida albicans and compared with fluconazole and nystatin as reference drug. Some of the compounds have exhibited potent inhibitory activity
on all fungal strains, and were found more potent than reference standard. Some of the important structural features required
for broad spectrum activity in this series have been derived. 相似文献
17.
V. L. Gein T. M. Zamaraeva A. A. Kurbatova E. V. Voronina M. I. Vakhrin 《Pharmaceutical Chemistry Journal》2010,44(7):366-369
N,7-Diaryl-5-methyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxamides were synthesized by three-component reaction of acetoacetanilides (2-methylacetoacetanilide, 2,4-dimethylacetoacetanilide,
4-chloroacetoacetanilide, o-acetoacetanilide) with a mixture of aromatic aldehyde and 5-aminotetrazole. The proposed structures are confirmed by IR and
PMR spectroscopy and mass spectrometry. The synthesized compounds are characterized with respect to antimicrobial activity. 相似文献
18.
When boiled pork extract was heated under reflux at 102 °C for 4 hr mutagens, which were detected using Salmonella typhimurium strains TA98 and TA1538, were formed. The level of mutagenicity was dependent on the concentration of pork in the extract, the duration of boiling and on pH; the optimum pH for mutagen formation was found to be 9 to 11. Thin-layer chromatographic analysis showed that the mutagens formed in boiled pork extract were chromatographically distinguishable from benzo[a]pyrene and from the primary mutagenic pyrolysis products of tryptophan (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and of glutamic acid (2-amino-6-methyldipyrido[1,2−a:3′,2′-d]imidazole) 相似文献
19.
Heterocycles via Mannich Bases, VII: Synthesis of Pyrazolo[1,5-a]pyrido[2,3-d]pyrimidin-9(4H)-ones The title compounds 4 are synthesised from 5-amino-3-methylpyrazolo[1,5-a]pyrimidin-7(4H)-one (2) and ketone Mannich bases or dehydro Mannich bases. 相似文献
20.
《Il Farmaco; edizione pratica》2003,57(12):959-971
Synthesis applied to prepare compounds 5–15 and 17–22 discussed in this paper has been presented in Scheme 1. Multi-stage preparation techniques were used to obtain 4-aryl-hexahydro 1–4 and (R,R) and (S,S) 4-aryl-octahydropyrido[1,2-c]pyrimidine-1,3-dione (16) derivatives, being the starting compounds for further modification. N-Alkylation of the imide group in compounds 1–4 and 16 followed, using 1,4-dibromobutane to yield monobromobutyl derivatives 5–8 and 17. Subsequent condensation of those compounds with appropriate 1-aryl or 1-heteroarylpiperazine led to the final hexahydro- 9–15 and octahydro- 18–22 pyrido[1,2-c]pyrimidine-1,3-dione derivatives. The final products were subjected to screening test to elucidate the affinity to 5-HT1A and 5-HT2A receptors. 相似文献