Multicomponent Reactions of Acetoacetanilide Derivatives with Aromatic Aldehydes and Cyanomethylene Reagents to Produce 4H-Pyran and 1,4-Dihydropyridine Derivatives with Antitumor Activities (original) (raw)
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Medicinal Chemistry, 2012
Two series of compounds with the general formula of 4,6-diaryl-2-oxo-1,2 dihydropyridine-3carbonitriles and their isosteric imino derivatives were synthesized through a one pot reaction of acetophenone, aldehyde and ammonium acetate with ethyl cyanoacetate or malononitrile, respectively. The synthesized compounds were evaluated for tumor cell growth inhibitory using the human HT-29 colon and MDA-MB-231 breast tumor cell lines. Compound 4-(2-Ethoxyphenyl)-2-imino-6-(4-fluorophenyl)-1,2-dihydropyridine-3 carbonitrile (6) showed IC 50 value of 0.70 μM versus HT-29. Meanwhile, compound 4-(2-Hydroxyphenyl)-2-imino-6-(4fluorophenyl)-1,2-dihydropyridine-3-carbonitrile (4) showed IC 50 value of 4.6 μM versus MDA-MB-231. Docking compound 10 to possible molecular targets, survivin and PIM1 kinase showed appreciable interactions with both, which suggest possible targets for the antitumor activity of this novel class of anticancer compounds.
Molecules (Basel, Switzerland), 2015
1-(2,4-Dichlorophenyl)-3-(4-fluorophenyl)propen-1-one (1) was prepared and reacted with an active methylene compound (ethyl cyanoacetate) in the presence of ammonium acetate to give the corresponding cyanopyridone 2. Compound 2 reacted with hydrazine hydrate, malononitrile, ethyl bromoacetate and phosphorous oxychloride to afford compounds 4 and 7-11, respectively. The 2-chloropyridine derivative 11 reacted with different primary amines, namely benzyl amine, piperonyl amine, 1-phenylethyl amine, and/or the secondary amines 2-methyl-pipridine and morpholine to give the corresponding derivatives 12-15. Hydrazinolysis of chloropyridine derivative 11 with hydrazine hydrate afforded the corresponding hydrazino derivative 17. Condensation of compound 17 with ethyl acetoacetate, acetylacetone, isatin and different aldehydes gave the corresponding derivatives 18-21. Some of newly synthesized compounds were screened for cytotoxic activity against three tumor cell lines. The results indicated...
Synthesis and Evaluation of New Series of 1,4-Dihydropyridine Derivatives as Anticancer Agents
International Journal of Sciences: Basic and Applied Research, 2016
1,4-dihydropyridine derivatives represent one of the important classes of compounds possessing a wide variety of biological activities including anticancer activity. In the present study, (4-Alkyl/Aryl-1-substituted 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxilicacid, 3,5-bis [2(aminothioxomethyl)hydrazides]) (6 a-l) were synthesized by the reaction of 4-alkyl/aryl-3,5-dicarboalkoxy-2,6-dimethyl-1,4-dihydropyridines (4 a-l) with thisemicarbazide and evaluated for their anti-cancer properties. All the synthesized compounds were characterized by IR, NMR and Mass spectra and were screened to evaluating for anticancer activity against three cell lines (MCF-7, HeLa and Hep G 2 ) by using MTT assay method. The results showed that compounds 6j and 6l showed significant cytotoxicity with IC 50 values ranging from 56µM - 74µM.
Archiv der Pharmazie, 2010
A series of twenty new 4‐substituted‐2,6‐dimethyl‐3,5‐bis‐N‐(heteroaryl)‐carbamoyl‐1,4‐dihydropyridines have been prepared from a three‐component one‐pot condensation reaction of N‐heteroaryl acetoacetamide, an aromatic/heteroaromatic aldehyde, and ammonium acetate under four different experimental conditions. Except for the conventional method, all the experimental conditions were simple, eco‐friendly, economical, and the reactions were rapid and high‐yielding. The methods employed have been compared in terms of yields, cost, and simplicity. The synthesized compounds were characterized by different spectroscopic techniques and evaluated for their in‐vitro anticancer, antibacterial, and antitubercular activities. Amongst the compounds tested, compound 25 exhibited the highest anticancer activity while compounds 14 and 18 exhibited significant antibacterial and antitubercular activities.
Two series of novel substituted 1,4-dihydropyridine derivatives incorporating nitrogen mustard pharmacophore hybrids without spacer DHP-M (4a–4d) and with ethyl spacer DHP-L-M (8a–8g) were designed and synthesized. They were subjected to in silico ADME prediction study to check their drug-like properties and evaluated for their cytotoxicity against: A 549 (lung), COLO 205 (colon), U 87 (glioblastoma), and IMR-32 (neuroblastoma) human cancer cell lines in vitro using 3-(4,5- dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay against chlorambucil and docetaxel. Majority of the test compounds exhibited moderate to significant cytotoxic activity. The highest activity in all the investigated cancer cells was displayed by DHP-M (4a). This may be due to the less steric hindrance offered by 4a.
ChemistrySelect, 2018
In this study, we explored the catalyst-free one-pot multicomponent synthesis of 1,4-dihydropyridine derivatives by following green chemistry protocol. The present approach shows the significant outcomes such as yield up to 94%, catalyst-free reaction, easy workup procedure and shorter period of reaction time. In this work we also highlighted the comparison of the yields obtained under both neat and solvent media as well. The anti-proliferative activity of all newly synthesized compounds has been assessed against six human solid tumor cell lines. Seven compounds show good activity against single cell line whereas, compounds having a pyridine scaffold showed significant anti-proliferative activity.
A number of 1,4-dihydropyridine derivatives (9a-d, 10a-d and 11a-d) were designed and synthesized by the reaction of 1,3,4-oxadiazole-5-thiones and 1,2,4-triazole-5-thiones to 2,6-dibromomethyl-3,5-diethoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridine. The synthesized compounds were characterized using FT-IR, 1 H-NMR, 13 C-NMR spectral data, ESI-MS and elemental analysis. The cytotoxicity of the synthesized compounds was evaluated in human breast cancer (MCF-7) cells based on the results of MTT assay. The results indicated that compound diethyl 4-(3-nitrophenyl)-2,6-bis[((5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl)thio)methyl]-1,4-dihydro pyridine-3,5-dicarboxylate (9b) with (IC 50 = 23±2.32 µM) was the most potent derivative against MCF-7 cells. Based on the results, the use of oxadiazole moiety in the C2 and C6 positions of 1,4-dihydropyridine ring system enhanced the cytotoxic potential of these derivatives. Therefore, some of the oxadiazole-substituted 1,4-DHPs may facilitate further modifications which result in the discovery of potent cytotoxic agents.
Molecules, 2011
The title compounds were prepared by reaction of 6-acetyltetralin (1) with different aromatic aldehydes 2a-c, namely 2,6-dichlorobenzaldehyde, 2,6-diflourobenzaldehyde, and 3-ethoxy-4-hydroxybenzaldehyde, to yield the corresponding α,β-unsaturated ketones 3a-c. Compound 3b was reacted with hydrazine hydrate to yield the corresponding 2-pyrazoline 4, while compounds 3a,b reacted with thiourea to afford the 2-thioxopyrimidine derivatives 5a,b, respectively. The reaction of 1, and the aromatic aldehydes 2a-c with ethyl cyanoacetate, 2-cyano-thioacetamide or malononitrile in the presence of ammonium acetate yielded the corresponding 2-oxopyridines 6a,b, 2-thioxopyridines 7a-c or 2-iminopyridines 8a,b, respectively. The newly prepared compounds were evaluated for anticancer activity against two human tumor cell lines. Compound 3a showed the highest potency with IC 50 = 3.5 and 4.5 μg/mL against a cervix carcinoma cell line (Hela) and breast carcinoma cell line (MCF7), respectively.
Anticancer activities of some newly synthesized pyridine, pyrane, and pyrimidine derivatives
Bioorganic & Medicinal Chemistry, 2006
A series of pyridine, pyrane, and pyrimidine derivatives (2-11) were newly synthesized using nitrobenzosuberone 1 as a starting material. The antitumor activities of the synthesized compounds were evaluated utilizing 59 different human tumor cell lines, representing leukemia, melanoma, lung, colon, brain, ovary, breast, prostate as well as kidney. Some of the tested compounds especially 2, 3, 4c, 6, 7, 9b, 10a, and 11 exhibited better in vitro antitumor activities at low concentration (log 10 GI 50 = À4.7) against the used human tumor cell lines. Additionally, compounds 3, 4c, 6, 7, and 9b were highly selective to inhibit leukemia cell lines. The detailed synthesis, spectroscopic data and antitumor properties for the synthesized compounds were reported.
Bioorganic & Medicinal Chemistry Letters, 2007
A series of trans-2-alkyl-4-halopiperidines and 2-alkyl-4-halo-1,2,5,6-tetrahydropyridines were prepared by means of an iron(III) catalyzed process. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780 (ovarian cancer), SW1573 (non-small cell lung cancer), and WiDr (colon cancer). The results on the biological activity revealed that, in general, the 2-alkyl-4-halo-1,2,5,6-tetrahydropyridine analogs are more potent than the trans-2-alkyl-4-halopiperidine derivatives. A remarkable selectivity of the aza compound 5f for the resistant cell line WiDr was observed. Cell cycle studies revealed a G 2 /M phase arrest for 5f.