Promising anti-breast cancer agents derived from substituted quinolines were discovered. The quinolines were readily synthesized in large scale from a sequence of reactions starting from 4-acetamidoanisole. The Michael addition product was isolated as the reaction intermediate in the ring closing reaction of 4-amino-5-nitro-2-(3-trifluoromethylphenyloxy)anisole with methyl vinyl ketone leading to 6-methoxy-4-methyl-8-nitro-5-(3-trifluoromethylphenyloxy)quinoline (14). The amino function of 8-amino-6-methoxy-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline, prepared from 14, was connected to various side chains via alkylation with N-(3-iodopropyl)phthalimide, Michael addition with acrylonitrile, and reductive amination with various heterocycle carboxaldehydes, such as imidazole-4-carboxaldehyde, thiophene-2-carboxaldehyde, and 2-furaldehyde. Effects of the substituted quinolines on cell viability of T47D breast cancer cells using trypan blue exclusion assay were examined. The results showed that the IC50 value of 6-methoxy-8-[(2-furanylmethyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline is 16 ± 3 nM, the lowest IC50 out of all the quinolines tested. IC50 values of three other quinolines are in the nanomolar range, a desirable range for pharmacological testing.
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Quinolines are known for their anti-malarial,– leishmanicidal, antibacterial and anticancer activities.– Recently, quinolines were examined in ATP-binding cassette drug transporter inhibition, targeting tumor hypoxia, modulation of multidrug resistance, and tyrosine kinase inhibition. Based on these literature results, we investigated substituted quinolines in search of novel anti-breast cancer compounds. After our initial anticancer screening, we focused on substituted quinolines with a skeletal structure derived from 8-amino-5-(aryloxy)-6-methoxy-4-methylquinoline, by derivatizing its C8-amino side chain. We report herein syntheses of new quinolines possessing amine, nitrile, imidate, amidine and heterocyclic functionalities in the C8-amino side chain, and their potent anti-breast cancer activities against T47D breast cancer cells. The synthetic substituted quinolines are summarzied in .
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T1 - Synthesis of 2,10-diphenyl-2H-pyridazino[4,5-b]quinolin-1-one and 2,3-dihydro-9-phenyl-2-phenylamino-1H-pyrrolo[3,4-b]quinolin-1-one derivatives as peripheral-type benzodiazepine receptor ligands
10631 1-Methyl-1H-pyrrole-2-carboxaldehyde : ..
Synthesis of 2-aryl-3-(thiophen-2-ylmethyleneamino) quinazolin-4(3H)-one: 3-Amino-2-substitutedphenyl quinazolin-4(3H)-one (0.008mole) was taken in a round bottomed flask containing absolute alcohol. Thiophene-2-carboxaldehyde (0.008mole) was added and the reaction mixture was refluxed with a catalytic amount of conc. H2SO4 for 5h. The contents were poured into a beaker containing crushed ice; the solid obtained was filtered, washed with water and recrystallized from ethanol.
2-Chloroquinol ine-3-carboxaldehyde, 2- ..
2,5-Dihydroxyacetophenones was the starting material for the synthesis of 5-Methoxy-2-hydroxyacetophenone which was in turn converted to 6- methoxy- 4- oxo- 4H- benzopyran- 3- yl-carboxaldehyde through Vilsmeier-Haack formylation in good yields (80-85%). First of all, 2,5-Dihydroxyacetophenone (3) was synthesized from hydroquinone. Hydroquinone (1) was converted to hydroquinone diacetate (2) through Friedel crafts acylation with acetic anhydride using sulphuric acid as catalyst. Dry hydroquinone diacetate was in turn gently heated with anhydrous aluminium chloride to give 2,5-Dihydroxyaceto phenone.
3-(2-FUROYL)QUINOLINE-2-CARBOXALDEHYDE | …
A mixture of 2,4-dihydroxybenzophenone 1.07 gm (0.005 M), 2-chloro-6-methoxyquinoline-3-carboxaldehyde 1.105 gm (0.005 M), various amides 0.30 gm (0.005 M) and EAN 30 ml (1 M) was refluxed with stirring at 80˚C temperature. The completion of reaction was monitored by TLC with using solvent system chloroform/methanol (v/v = 70:30). On completion of reaction, the reaction mixture was extracted thrice with 20 ml ethyl acetate. The extract was dried over anhydrous sodium sulfate, evaporated under vacuum and the residue was purified via recrystallisation from methanol or ethyl acetate to obtain pure new Mannich products 4(a-f) (Scheme 1).