14 research outputs found
Novel catalyst-free synthesis of some 3-alkylaminoquinoxaline-2(1H)-thiones and 3-alkyloxyquinoxaline-2(1H)-thiones in ethanol
No full textSeventeen 3-alkylaminoquinoxaline-2(1H)-thiones and 3-alkyloxyquinoxaline-2(1H)-thiones were prepared by a novel thionation protocol from the readily available quinoxaline-2,3-dione in excellent overall yields. This protocol starts with the chlorination of dione using thionyl chloride to give 2,3-dichloroquinoxaline followed by the reaction with equimolar amounts of N-nucleophiles (primary amines and secondary amines) or O-nucleophiles (phenols and alcohols) to principally afford 2-alkanamino-3-chloroquinoxalines or 2-alkyloxy-3-chloroquinoxalines, respectively. The chloroquinoxalines reacted with the thionation reagent N-cyclohexyl dithiocarbamate cyclohexyl ammonium salt in ethanol under reflux to principally give the corresponding quinoxalin-2-yl cyclohexylcarbamodithioate that finally rearranges in situ to give the corresponding thiones in 76-93% overall yields. Our novel catalyst-free synthesis of some 3-alkylaminoquinoxaline-2(1H)-thiones and 3-alkyloxyquinoxaline-2(1H)-thiones in ethanol protocol has many advantages compared with traditional methods: excellent yields, one-pot reaction, simple experimental procedure, and commercial availability of the required reagents. In addition, this method could be generalized to involve a wide range of amines, phenols, and alcohols, and also during the reaction, we did not notice a bad odor. The structures of synthesized compounds are elucidated via different methods such as 1H NMR, 13C NMR, elemental analysis, and MS.</p
Synthesis of <i>N</i>-alkyl-3-[2-oxoquinolin-1(2<i>H</i>)-yl]propanoic acid derivatives and related compounds: cytotoxicity and EGFR inhibition of some propanamide derivatives
No full textA series of 20 new structure-modified quinolin-2-one derivatives were prepared for biological evaluation. This was successfully achieved based on chemoselective reactions of heterocyclic amides with acrylic acid derivatives, which gave 3-[2-oxoquinolin-1-(2H)-yl] propanoic acid derivatives (N-substitution via a unique behavior). The ester was reacted with hydrazine to afford the corresponding hydrazide. Both the corresponding ester and hydrazide were used as building blocks to modify the quinolone structure and give N-hydroxyl propanamides, oxadiazoles, and thiosemicarbazides. The corresponding carboxylic acid and hydrazide were used to prepare several amides: N-alkyl-3-[2-oxoquinolin-1(2H)-yl]propanamides via azide and dicyclohexyl carbodiimide coupling methods. Among derivatives, compound 9e exhibited potent cytotoxicity against MCF-7 cells with an IC50 value of 1.32 μM compared to doxorubicin with an IC50 value of 1.21 μM. Additionally, it caused potent EGFR inhibition by 97% with an IC50 value of 16.89 nM compared to Erlotinib with an IC50 value of 29.8 nM. Finally, the binding mode of compound interactions toward EGFR was highlighted using a molecular docking study; compound 9e exhibited good binding affinity with a binding energy of −17.89 kcal/mol, and it formed H-bond interactions with Met 769 as the key amino acid of interaction. Accordingly, compound 9e may be developed as an EGFR-oriented chemotherapeutic antibreast cancer agent.</p
Synthesis of Heterocyclic Skeletons by the Reaction of N1-(2-Cyanophenyl)-benzimidoyl Chloride with Thioamides
No full textThe reaction of N-(2-cyanophenyl)benzimidoyl chloride with reagents containing a thioamide moiety, i.e. thioacetamide, benzylthiourea, symmetrical dialkyl- and diarylthioureas gave different cyclic products: 3,1-benzothiazine, 1,3,5-benzotriazocine and quinazoline. The reaction pathways of prepared compounds are discussed
One-Pot Quinazolin-4-yl-thiourea Synthesis via N-(2-Cyanophenyl) benzimidoyl isothiocyanate
No full text1-substituted-3-(2-phenylquinazolin-4-yl) thioureas (7) were produced by an intramolecular cycloaddition reaction of 1-substitued-3-[(2-cyanophenylimino) phenylmethyl] thioureas (3). These compounds in turn were prepared by the reaction of N-(2-cyanophenyl)benzimidoyl isothiocyanate (2) with primary amines. The structures of products 7 were confirmed by FTIR, 1H-NMR, 13C-NMR, mass spectroscopy and X-ray crystallography
Convenient syntheses of methyl 2-[2-(3-acetyl-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)acetamido] alkanoates and their O-regioisomers
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Transformation of Amides to Thioamides Using an Efficient and Novel Thiating Reagent
No full textA convenient protocol was developed for the transformation of N-aryl-substituted benzamides to N-aryl-substituted benzothioamides using N-isopropyldithiocarbamate isopropyl ammonium salt as a novel thiating reagent. The major advantages of this protocol are its one-pot procedure, short reaction times, mild conditions, simple work-up, high yields and pure products
Facile Synthesis of Some Coumarin Derivatives and Their Cytotoxicity through VEGFR2 and Topoisomerase II Inhibition
No full textNovel semisynthetic coumarin derivatives were synthesized to be developed as chemotherapeutic anticancer agents through topoisomerase II, VEGFR2 inhibition that leads to apoptotic cancer cell death. The coumarin amino acids and dipeptides derivatives were prepared by the reaction of coumarin-3-carboxylic acid with amino acid methyl esters following the N,N-dicyclohexylcarbodiimide (DCC) method and 1-hydroxy-benzotriazole (HOBt), as coupling reagents. The synthesized compounds were screened towards VEGFR2, and topoisomerase IIα proteins to highlight their binding affinities and virtual mechanism of binding. Interestingly, compounds 4k (Tyr) and 6c (β-Ala-L-Met) shared the activity towards the three proteins by forming the same interactions with the key amino acids, such as the co-crystallized ligands. Both compounds 4k and 6c exhibited potent cytotoxic activities against MCF-7 cells with IC50 values of 4.98 and 5.85 µM, respectively causing cell death by 97.82 and 97.35%, respectively. Validating the molecular docking studies, both compounds demonstrated promising VEGFR-2 inhibition with IC50 values of 23.6 and 34.2 µM, compared to Sorafenib (30 µM) and topoisomerase-II inhibition with IC50 values of 4.1 and 8.6 µM compared to Doxorubicin (9.65 µM). Hence, these two promising compounds could be further tested as effective and selective target-oriented active agents against cancer
