15589-58-9Relevant academic research and scientific papers
One-step Synthesis of 3-Unsubstituted 4-Hydroxy-2(1H)-Quinoline
Menglin, Ma,Qingrong, Sun,Weiqing, Yang,Xingyi, Wang,Yinan, Xu
, p. 435 - 441 (2021/11/22)
3-Unsubstituted 4-hydroxy-2(1H)-quinolone (DHQ) derivatives were synthesized from aniline derivatives and diethyl malonate at low temperature using AlCl3 as catalyst and Eaton reagent as acidic environment. A reaction mechanism was proposed and elucidated. Different synthetic intermediates are specially prepared or purified and used to understand the reaction and validation mechanism.
Highly Enantioselective Synthesis of Functionalized Glutarimide Using Oxidative N-Heterocyclic Carbene Catalysis: A Formal Synthesis of (?)-Paroxetine
Porey, Arka,Santra, Surojit,Guin, Joyram
supporting information, p. 5313 - 5327 (2019/04/16)
A simple yet highly effective approach toward enantioselective synthesis of trans-3,4-disubstituted glutarimides from readily available starting materials is developed using oxidative N-heterocyclic carbene catalysis. The catalytic reaction involves a formal [3 + 3] annulation between enals and substituted malonamides enabling the production of glutarimide derivatives in a single chemical operation via concomitant formation of C-C and C-N bonds. The reaction offers easy access to a broad range of functionalized glutarimides with excellent enantioselectivity and good yield. Synthetic application of the method is demonstrated via formal synthesis of (?)-paroxetine and other bioactive molecules.
Lanthanum(III)-Catalyzed Three-Component Reaction of Coumarin-3-carboxylates for the Synthesis of Indolylmalonamides and Analysis of Their Photophysical Properties
Jennings, Julia J.,Bhatt, Chinmay P.,Franz, Annaliese K.
, p. 6211 - 6222 (2016/08/16)
New methodology has been developed for the Lewis acid catalyzed synthesis of malonamides. First, the scandium(III)-catalyzed addition of diverse nucleophiles (e.g., indoles, N,N-dimethyl-m-anisidine, 2-ethylpyrrole, and 2-methylallylsilane) to coumarin-3-carboxylates has been developed to afford chromanone-3-carboxylates in high yields as a single diastereomer. Upon investigating a subsequent lanthanum(III)-catalyzed amidation reaction, a new multicomponent reaction was designed by bringing together coumarin-3-carboxylates with indoles and amines to afford indolylmalonamides, which were identified to exhibit fluorescent properties. The photophysical properties for selected compounds have been analyzed, including quantum yield, molar absorptivity, and Stokes shift. Synthetic studies of several reaction byproducts involved in the network of reaction equilibria for the three-component reaction provide mechanistic insight for the development of this methodology.
Synthesis of symmetrically substituted 3,3-dibenzyl-4-hydroxy-3,4-dihydro- 1H-quinolin-2-ones, as novel quinoline derivatives with antibacterial activity
Ferretti, Matías D.,Neto, Alexandre T.,Morel, Ademir F.,Kaufman, Teodoro S.,Larghi, Enrique L.
, p. 253 - 266 (2014/06/09)
A novel series of symmetrically substituted 3,3-dibenzyl-4-hydroxy-3,4- dihydro-1H-quinolin-2-ones was synthesized and tested as antimicrobials. The minimum inhibitory concentration (MIC) values of the most active heterocycles were slightly higher than those exhibited by levofloxacin, employed as comparator. Structural factors affecting the activity were explored along three diversification points, including the substituents of the aromatic rings of the 3-benzyl moieties, as well as the functionalization of both, the homocyclic ring of the heterocycle and the quinolonic nitrogen atom. 6-Chloro and 3,3-bis(4′-chlorobenzyl) derivatives showed the lower MIC values. Optimally substituted heterocycles were synthesized, which exhibited enhanced activity.
6-methoxy-2-oxo-1,2-dihydroquinoline-3,4-dicarbonitriles, a red compound class with solvent and pH independent green fluorescence maxima
Enoua,Lahm,Uray,Stadlbauer
, p. 492 - 501 (2014/04/17)
The sodium p-toluenesulfinate mediated reaction of potassium cyanide with 4-chlorocarbostyrils 8, 16, 18, and 23 gave in all cases the highly fluorescent and stable 6-methoxy-2-oxoquinoline-3,4-dicarbonitrile 9 (λexc 460 nm and λem 545 nm). This is remarkable, because starting carbostyrils 8, 16, 18, and 23 had a chloro substituent, a nitro substituent, an acetylamino substituent, or a piperidinyl substituent in position 3. Hence, we observed not only a substitution of the 4-chloro and expected 3-chloro substituents by the cyanide nucleophile but also an exchange of a nitro substituent, an acetylamino substituent, and a piperidinyl substituent in position 3. The multistep insertion of substituents leading to 8, 16, 18, and 23 started from 4-hydroxy-6-methoxyquinolone 4, easily obtained from p-anisidine and malonic acid. Substitutions in position 3 gave 4-hydroxy-3-nitro and 3-chloro intermediates, which were converted to 3,4-dichlorocarbostyril 8 and 4-chloro-3-nitrocarbostyril 16. Reduction of the 3-nitro intermediate led to the 3-acetylamino analog and subsequent chlorination led to 3-acetylamino-4- chlorocarbostyril 18. 4-Chloro-3-piperidinylcarbostyril 23 was obtained from intermediate 3,3-dichloroquinolinedione by subsequent amination, reduction and chlorination. Further, 3-acetylamino-4-chlorocarbostyril 18 gave with lithium p-toluenesulfinate highly fluorescent 3-amino-6-methoxy-4-p- tolylsulfonylquinolone 19.
Ligand-based modelling followed by synthetic exploration unveil novel glycogen phosphorylase inhibitory leads
Habash, Maha,Taha, Mutasem O.
experimental part, p. 4746 - 4771 (2011/09/20)
Glycogen phosphorylase (GP) is a valid anti-diabetic target. Accordingly, we applied a drug discovery workflow to unveil novel inhibitory GP leads via combining pharmacophore modeling, QSAR analysis and in silico screening, followed by synthetic exploration of active hits. Virtual screening identified six low micromolar inhibitory leads from the National Cancer Institute (NCI) list of compounds. The most potent hits exhibited anti-GP IC50 values of 3.2 and 4.1 μM. Synthetic exploration of hit 59 (IC50 = 4.1 μM) yielded 25 lead inhibitors with the best illustrating IC50 of 3.0 μM. Interestingly, we prepared several novel mixed oxalyl amide anti-GP leads employing new chemical reaction involving succinic acid-based adducts.
Design and synthesis of bis-amide and hydrazide-containing derivatives of malonic acid as potential HIV-1 integrase inhibitors
Sechi, Mario,Azzena, Ugo,Delussu, Maria Paola,Dallocchio, Roberto,Dessi, Alessandro,Cosseddu, Alessia,Pala, Nicolino,Neamati, Nouri
experimental part, p. 2442 - 2461 (2009/04/05)
HIV-1 integrase (IN) is an attractive and validated target for the development of novel therapeutics against AIDS. In the search for new IN inhibitors, we designed and synthesized three series of bis-amide and hydrazide-containing derivatives of malonic acid. We performed a docking study to investigate the potential interactions of the title compounds with essential amino acids on the IN active site.
A CONVENIENT APPROACH TO THE SYNTHESIS OF PRENYL-, FURO- AND PYRANO-QUINOLINE ALKALOIDS OF THE RUTACEAE
Shobana, N.,Yeshoda, P.,Shanmugam, P.
, p. 757 - 762 (2007/10/02)
A convenient method for the synthesis of 4-hydroxy-3-prenyl-2-quinolones, wjich have been recognised as precursors to prenyl-, furo- and pyranoquinoline alkaloids of the Rutaceae is described.The methodology involves C,C-diprenylation of 2,4-dihydroxyquinoline followed by partial deallylation using sodium hydrogen telluride reagent.
Prostaglandin-H Synthase Inhibition by Malonamides. Ring-Opened Analogues of Phenylbutazone
Vennerstrom, Jonathan L.,Holmes, Thomas J.
, p. 434 - 437 (2007/10/02)
Recent reports of serious concern regarding the sfe clinical use of phenylbutazone and its hydroxylated metabolite (oxyphenbutazone) as antiinflammatory agents have prompted the further investigation of ring-opened (malonamide) derivatives as potentially preferable therapeutic derivatives.Earlier reports have claimed reduced toxicity among similar derivatives.These studies reveal the relative degree of prostaglandin-H (PGH) synthase inhibitory activity among a series of malonamide derivatives.Contrary to observations in the pyrazolidinedione series, incorporation of a nonpolar butyl side chain in these malonamides was not beneficial but, rather, detrimental to enzyme-inhibitory activity.Although nine of the reported nonbutylated malonamides was a potent an inhibitor of this enzyme as phenylbutazone, they all showed some inhibitory activity.PGH synthase inhibitory activity was especially pronounced in the bis(p-hydroxy anilide) derivatives, even extending to succinamide and adipamide derivatives.Of some interest is the observation that all of these p-hydroxy anilide derivatives were more potent inhibitors of this enzyme than acetaminophen.
Reaction of malondiamides with disulfur dichloride: a reinvestigation
Kutney, Gerald W.,Still, Ian W.J.
, p. 1233 - 1238 (2007/10/02)
The reaction of a series of N,N'-dialkyl and N,N'-diaryl malondiamides with disulfur dichloride have been reinvestigated.The claim, made almost 60 years ago, that the products of this reaction are dithioketones R2CS2, is shown to be unfounded.The structures of these products are shown to be the symmetrically substituted 1,2,4,5-tetrathianes, 8a-e.-
