Convenient synthesis of some methyl-N-[2-(3-oxo-6-p-tolyl-2,3,4,5-tetrahydropyridazin-2-yl)-acetylamino]amino acid esters

Rayes, S. M. El

doi:10.3998/ark.5550190.0009.g23

Cited by 12 publications

(4 citation statements)

References 17 publications

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“…Our research team quickly discovered that chemoselective alkylation of amides and thioamides could be regulated. − We agreed to extend our results to the structure modification of 2-phenyl-2,3-dihydrophthalazine-1,4-dione ( 1 ), our model heterocyclic amide, as a follow-up to these studies. The single O-substituted result of the reaction of model ambient nucleophile 1 with ethyl chloroacetate in acetone in the presence of K 2 CO 3 under reflux for 12 h was (4-oxo-3-phenyl-3,4-dihydro-phthalazin-1-yloxy)acetic acid ethyl ester ( 2 ).…”

Section: Resultsmentioning

confidence: 55%

Synthesis of Novel Phthalazinedione-Based Derivatives with Promising Cytotoxic, Anti-bacterial, and Molecular Docking Studies as VEGFR2 Inhibitors

et al. 2022

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The parent ester methyl-3-[2-(4-oxo-3-phenyl-3,4-dihydro-phthalazin-1-yloxy)-acetylamino] has 18 compounds. The starting material for alkanoates, their corresponding hydrazides, hydrazones, and dipeptides were produced by chemoselective O-alkylation of 2-phenyl-2,3-dihydrophthalazine-1,4-dione with ethyl chloroacetate(4-oxo-3-phenyl-3,4-dihydro-phthalazin-1-yloxy) acetic acid methyl ester. The starting ester was hydrazinolyzed, then azide coupled with amino acid ester hydrochloride to produce several parent esters, and then hydrazinolyzed to produce parent hydrazides. These hydrazides were used to make a series of dipeptides by reacting them with amino acid ester hydrochloride under azide coupling conditions, and they were also condensed with a number of aldehydes to make the hydrazones. These derivatives were subjected to cytotoxicity against HCT-116 and MDA-MB-231 cells and anti-bacterial and molecular docking studies. Results indicated that the tested compounds, especially 7c and 8b with the phenyl phthalazinone moieties, had promising cytotoxicity against the HCT-116 cells with IC 50 values of 1.36 and 2.34 μM, respectively. Additionally, the promising compounds 7c and 8b exhibited poor cytotoxicity against WISH cells with much higher IC 50 values, so they were safe against normal cells. Compound 8c exhibited potent anti-bacterial activity with inhibition zones of 12 and 11 mm against Staphylococcus aureus and Escherichia coli , respectively. The molecular docking results of compounds 7c and 8b revealed a good binding disposition and the ligand–receptor interactions like the co-crystallized ligand of the VEGFR2 protein, which may be the proposed mode of action. Finally, compounds 7c and 8b exhibited good ADME pharmacokinetics with good drug-likeness parameters. Hence, detailed studies for the mechanism of action of such compounds are highly recommended for the development of new potent anti-cancer and anti-bacterial agents.

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Section: Resultsmentioning

confidence: 55%

Synthesis of Novel Phthalazinedione-Based Derivatives with Promising Cytotoxic, Anti-bacterial, and Molecular Docking Studies as VEGFR2 Inhibitors

et al. 2022

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“…Similarly, 3 was also formed by diazotization of anthranilhydrazide 4 in a moderate yield. Benzotriazinone 3 was reacted with methyl chloroacetate in DMF in the presence of potassium carbonate at 100 °C to give the chemoselective N -alkylated ester, methyl-2-(4-oxobenzotriazin-3(4 H )-yl)acetate 6a as the only product on the basis of chemoselective reactivity of heterocyclic amides toward electrophiles, Scheme . − The multistep reactions mentioned gave 6a in an overall high yield from available isatoic anhydride, but the alkyl halides needed to prepare other methyl-2-(4-oxobenzotriazin-3(4 H )-yl)alkanoates 6b – c were not available.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Activities of Some New Benzotriazinone Derivatives Based on Molecular Docking; Promising HepG2 Liver Carcinoma Inhibitors

et al. 2020

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In one-pot strategy, diazotization of methyl anthranilate 5 followed by addition of amino acid ester hydrochloride, we have prepared methyl-2-(4-oxobenzotriazin-3(4H)-yl)alkanoates 6a−c. Starting with hydrazides 7a,b, N-alkyl-2-(4-oxobenzotriazin-3(4H)-yl)alkanamides 9−10(a−h) and methyl-2-(2-(4-oxobenzotriazin-3(4H)-yl)alkanamido)alkanoates 11−12(a−e) were prepared via azide coupling. Hydrazones 13−15 were prepared via condensation of hydrazides 7a,b with 4-methoxybenzaldehyde, 4-dimethylaminobenzaldehyde, and/or arabinose. Molecular docking was done for synthesized compounds using MOE 2008-10 software. The compounds 9a, 12a, 12c, 13a, 13b, and 14b have the most pronounced strong binding affinities toward the target E. coli Fab-H receptor, whereas compounds 3, 11e, 12e, and 13a have the most pronounced strong binding affinities toward the target vitamin D receptor. The in vitro antibacterial activities of the highest binding affinity docked compounds were tested against E. coli, Staphylococcus aureus, and Salmonella spp. Majority of the tested compounds showed effective positive results against E. coli, while they were almost inactive against Staphylococcus aureus and Salmonella spp. The in vitro cytotoxic activities of the highest binding affinity-docked compounds were tested against the human liver carcinoma cell line (HepG2). Some compounds showed potent cytotoxic activity with low IC 50 values, especially for 3 (6.525 μM) and 13a (10.97 μM) than that for standard drug doxorubicin (2.06 μM).

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“…This ambident nucleophile 3 as all heterocyclic amides is considered as a mixture of tautomeric forms 3 a and 3 b and consequently contains two competing nucleophilic sites N and O , to react with electrophiles, Scheme 1. Earlier results reported by our group related to reaction of heterocyclic amides with electrophiles giving rise to either O ‐ substituted, [14] N ‐ substituted [15,16] or both O ‐ substituted and N ‐ substituted reaction products [17,18]…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Anti proliferative Activity of New N‐Pentylquinoxaline carboxamides and Their O‐Regioisomer

et al. 2020

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We have designed a series of quinoxalinepeptidomimetic derivatives based on our previous reported scaffold in attempt to find a promising lead compound. Quinoxaline derivatives; Nalkyl-3-(3-oxo-4-pentyl-3,4-dihydro-quinoxalin-2-yl)-propanamides and methyl 2-[3-(3-oxo-4-pentyl-3,4-dihydro-quinoxalin-2-yl)propanamido]alkanoates and their O-regioisomers were prepared by alkylation of the ambient nucleophile methyl 3-(3oxo-3,4-dihydroquinoxalin-2-yl)propanoate with pentyl bromide to give the corresponding N-and O-pentylquinoxaline ester derivatives. The N-and O-pentyl-quinoxaline ester derivatives gave the desired products by the reaction with amines and amino acid esters via azide coupling method. We have examined the anti proliferative activity of the 35 different synthesized compounds on human HCT-116 and HEK-293 cell lines. Out of 35 screened derivatives, 14 active compounds exhibited inhibitory action on the HCT-116 cells with IC 50 values ranging from 0.43 mM to 2.62 mM. We have also examined the impact of these active compounds on cancer cells nucleus and caspase 3 activity, we have the found that active compounds also increased in the caspase 3 activity which led to programmed cell death of cancer cells. We have also examined the impact of 35 compounds on the normal and non-cancerous cells (HEK-293) and we have found these active compounds did not cause any cytotoxic effect on the normal cells.

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Convenient synthesis of some methyl-N-[2-(3-oxo-6-p-tolyl-2,3,4,5-tetrahydropyridazin-2-yl)-acetylamino]amino acid esters

Cited by 12 publications

References 17 publications

Synthesis of Novel Phthalazinedione-Based Derivatives with Promising Cytotoxic, Anti-bacterial, and Molecular Docking Studies as VEGFR2 Inhibitors

Synthesis of Novel Phthalazinedione-Based Derivatives with Promising Cytotoxic, Anti-bacterial, and Molecular Docking Studies as VEGFR2 Inhibitors

Synthesis and Biological Activities of Some New Benzotriazinone Derivatives Based on Molecular Docking; Promising HepG2 Liver Carcinoma Inhibitors

Synthesis and Anti proliferative Activity of New N‐Pentylquinoxaline carboxamides and Their O‐Regioisomer

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