Dione Derivatives Research Articles

ChemInform Abstract: An Efficient Ultrasound Promoted One‐Pot Three‐Component Synthesis and Antibacterial Activities of Novel Pyrimido[4,5‐b]quinoline‐4,6(3H,5H,7H,10H)‐dione Derivatives.

AbstractThe reaction of 6‐aminothiouracil with the heteroaromatic aldehydes and cyclohexanedione or dimedone affords the target compounds.

ChemInform Abstract: An Efficient and Convenient Method for Synthesizing New Derivatives of Pyrido[2,3‐e]pyrrolo[1,2‐a][1,4]diazepine‐5,10‐dione via Sonogashira, Suzuki—Miyaura, and Stille Cross‐Coupling Reactions.

AbstractThe chiral diazepine dione derivative (III) is used as starting material for the synthesis of a variety of 3‐substituted derivatives, which represent bioisosteres of the anthramycin scaffold.

L-Proline-catalysed three-component Cascade Reaction for the Facile Synthesis of 3,4-dihydro-2H-pyrano[3,2-c]quinolin-2,5(6H)-dione Derivatives

A series of 4-aryl-3,4-dihydro-2 H-pyrano[3,2- c]quinolin-2,5(6 H)-dione derivatives was synthesised by the three-component reaction of aromatic aldehyde, quinoline-2,4-diol and Meldrum's acid catalysed by l-proline. This protocol has the advantages of easy work-up, mild reaction conditions and high yields.

Catalytic Stereoselective Conjugate Addition of Oxindole to Electron‐Deficient Alkynes

AbstractA Z/E‐selective and enantioselective conjugate addition of oxindoles to butyl but‐2‐ynedioate derivatives has been developed, providing a facile access to enantioenriched multifunctional olefins, which can be further converted into 3,3a‐ dihydro‐2H‐pyrrolo[3,4‐c]quinoline‐1,4(5H,9bH)‐dione derivatives via conventional operations.

Quinazoline-2,4( $$1H,3H$$ )-diones inhibit the growth of multiple human tumor cell lines

Quinazoline-2,4(1H, 3H)-diones exhibit a wealth of biological activities including antitumor proliferation. We established an improved method for the synthesis of quinazoline-2,4(1H, 3H)-dione derivatives with three points of molecular diversity. Data indicate that compounds 60 (average logGI50=−6.1), 65 (average logGI50=−6.13), 69 (average logGI50 = −6.44), 72 (average logGI50 = −6.39), and 86 (average logGI50 = −6.45) significantly inhibited the in vitro growth of 60 human tumor cell lines tested. Structure–activity relationship analyses indicate that chlorophenethylureido is the necessary substituent at the D3 diversity point (7-position of quinazoline-2,4(1H, 3H)-dione), in particular, o-chlorophenethylurea (69) achieved optimal activity. o- or m-Chlorophenethyl substitutions (69 and 72) at the D2 diversity point (3-position of quinazo line-2,4(1H, 3H)-dione) gave the most potent compounds. Methoxyl and 4-methylpiperazin-1-yl substitution at the D1 diversity point (6-position of quinazoline-2,4(1H, 3H)-dione skeleton) may yield better activity than other groups. The quinazoline-2,4(1H, 3H)-dione scaffold can be effectively replaced by 2H-benzo[b][1,4]thiazin-3(4H)-one.

Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H) and their docking and urease inhibitory activity

BackgroundA straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported.ResultsReactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 μM).DiscussionThe compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

Lack of human immunodeficiency virus-1 integrase inhibitory activity of novel 3a, 4, 7, 7a-tetrahydro-1H-isoindole-1,3 (2H)-dione derivatives

Background: Majority of reported integrase (IN) inhibitors had an important structural feature, i.e., 1,3-diketo functional group. It plays a vital role in IN inhibition by the formation of chelating triod with Mg +2 ions. Materials and Methods: A novel series of fifteen 3-(1,3-dioxo-3a, 4-dihydro-1 H -isoindol-2 (3 H ,7 H ,7a H )-yl)- N -(substituted phenyl) propanamide 4(a-o) analogs were synthesized by reacting the corresponding 3-chloro- N -(substituted phenyl) propanamides 2(a-o) with 3a, 4,7,7a-tetrahydro-1 H -isoindole-1,3 (2H)-dione (3) in acetonitrile medium in the presence of potassium carbonate. Various substituted 3-chloro- N -(substituted phenyl) propanamides 2(a-o) were synthesized by treating appropriate substituted anilines 1(a-o) with 3-chloro propionyl chloride in dichloromethane as solvent in the presence of triethylamine as base. The synthesized compounds have been characterized on the basis of fourier transform infrared spectrophotometerproton nuclear magnetic resonance spectrophotometer, 1 H NMR, Mass spectral and Elemental Analysis. Results: All the synthesized compounds were evaluated for their human immunodeficiency virus (HIV)-1 INinhibitory activity. However, unlike other anti-IN agents, none of these molecules showed inhibition of either 3' processing, and strand transfer reactions of HIV-1 IN.

Synthesis and biological evaluation of highly functionalized dispiro heterocycles

A series of highly functionalized dispiro[3H-indole-3,2′-pyrrolidine-3′,3′′-piperidine]-2(1H),4′′-dione derivatives have been synthesized in good to excellent yields by one pot three-component 1,3-dipolar cycloaddition reaction of substituted isatin, sarcosine and 1-methyl-3,5-bis[(E)-arylidene]piperidin-4-one with high degree of chemo-, regio- and stereoselectivity. The structure and relative stereochemistry of cycloadducts were confirmed by single crystal X-ray diffraction as well as with the help of 1H, and 13C NMR spectroscopic techniques. All the synthesized compounds were subjected to in vitro antimicrobial activity against various bacteria and fungi using broth microdilution method and antitubercular activity was carried out against Mycobacterium tuberculosis H37Rv strain using Lowenstein–Jensen medium. Some of the compounds emerged as good antimicrobials and reasonable antituberculars compared to standard drugs.

Synthesis and reactivity of 5-polyfluoroalkyl-5-deazaalloxazines

Reaction of 6-arylamino-1,3-dialkyluracils with anhydrides of polyfluorocarboxylic acids in the presence of pyridine and subsequent cyclization with concentrated H2SO4 gave the corresponding 1,3-dialkyl-5-(polyfluoroalkyl)pyrimido[4,5-b]quinoline-2,4(1H,3H)-diones (5-polyfluoroalkyl-5-deazaalloxazines). The reactivity of these compounds towards nucleophilic reagents, such as sodium cyanoborohydride, acetophenone, nitromethane, potassium cyanide, indole and p-thiocresol, as well as Suzuki and Sonogashira couplings are described. The nucleophilic addition takes place at the 5-position of the 5-deazaalloxazine system and is in many cases irreversible to give 5,10-dihydropyrimido[4,5-b]quinoline-2,4(1H,3H)-dione derivatives in good to excellent yields.

Synthesis of 1,3,1′,5′,6′,7′-hexahydro-3,3′-biindolyl-2,4′-dione derivatives by cyclization of 3-alkylideneoxindoles with enaminone

The reaction between 3-alkylideneoxindoles 1 and 3-aminocyclohex-2-enone 2 was studied, and an efficient synthesis of 1,3,1′,5′,6′,7′-hexahydro-3,3′-biindolyl-2,4′-dione derivatives was developed by a sequential Michael addition followed by intramolecular condensation catalyzed by nickel dichloride hexahydrate. The reaction mechanism is discussed.

Condensed sulfur-containing pyridine systems 3.* Construction of penta- and hexacyclic heterocyclic systems by the cascade reaction of 3-cyanopyridine-2(1H)-thiones and 3-cyano-pyridine-2(1H)-thiolates with 8-chloromethyl-3-methyl-7-(2-oxo-2-phenylethyl)xanthene

The alkylation of 3-cyanopyridine-2(1H)-thiones with 8-chloromethyl-3-methyl-7-(2-oxo-2-phenylethyl)- xanthene in a KOH–H2O–DMF system upon heating leads to the formation of pyrido-[3",2":4',5']thieno[3',2':5,6][1,4]diazepino[7,1-f]purine-2,4(3H,6H)-dione derivatives in good yields. Under milder conditions, the intermediates of the cascade reactions, namely, 2-({[3-methyl-2,6-dioxo-7-(2-oxo-2-phenylethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]methyl}thio)pyridine-3-carbonitriles, can be isolated and characterized.

Prediction of anti-tuberculosis activity of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dione derivatives

AbstractCorrelation analysis and, in particular, artificial neural networks (ANN) were used to predict the anti-mycobacterial activity of substituted 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones (PBODs) by quantitative structure — activity relationship (QSAR) calculations. Initially, sixty-four derivatives were synthesised and biologically tested; ten further derivatives were proposed for future synthesis on the basis of the prediction results. The biological activity was originally expressed by minimum inhibitory concentration (MIC) against Mycobacterium tuberculosis; however, its transformed pMIC form was found to be more informative. Theoretical molecular descriptors of several types were selected to establish a primary drug model of the species which was expected to exhibit a substantial anti-mycobacterial effect. Lipophilicity and solubility indices, several basic molecular properties, quantum chemistry quantities as well as 1H and 13C NMR chemical shifts, were employed as the descriptors, enabling a very successful prediction of the pMIC values. The utilisation of in silico variables and simulated NMR data is highly advantageous in the first phase of the drug design, as they permit prediction of the compounds with a high expected activity, minimising the risk of synthesising less active species. The MIC values predicted at less than 4 μmol L−1 for six of the ten compounds suggested for further synthesis are better than the best value for the original set of compounds.

ChemInform Abstract: 1‐Arylideneamino‐2,2,2‐trichloroethanols as Synthetic Equivalents of Arylideneimines in the Reaction with Cyclopropenone Derivatives.

AbstractThe title compounds (III) and (VII) react regiospecifically with cyclopropanones to give 2,2′‐diaryl‐tetrahydrobipyrrole‐3,3′‐dione derivatives.

ChemInform Abstract: A Stereoselective Synthesis of Symmetrical and Unsymmetrical Bibenzo[e][1,3]oxazine‐2,2′‐dione Derivatives Induced by Low‐Valent Titanium Reagent.

Abstract A series of symmetrical and unsymmetrical bibenzo[e][1,3]oxazine-2,2′-dione derivatives were synthesized by the reaction of various o-hydroxy Schiff bases and triphosgene induced by low-valent titanium reagent (TiCl4/Sm). A variety of substrates can participate in the process with good yields. The present method provides a useful preparation of 3,3′,4,4′-tetrahydro-4,4′-bibenzo[e][1,3]oxazine-2,2′-dione derivatives, which cannot be prepared otherwise. The mechanistic course of the reaction suggests the involvement of reduction, coupling, and cyclization by one-pot.

An Efficient Ultrasound Promoted One-Pot Three-Component Synthesis and Antibacterial Activities of Novel Pyrimido[4,5-b]quinoline- 4,6(3H,5H,7H,10H)-dione Derivatives

The reaction of 6-aminothiouracil with the heteroaromatic aldehydes and cyclohexanedione or dimedone affords the target compounds.

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

Dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives were prepared by successive N3- and N1-alkylation of hydantoins, followed by regioselective thionation and subsequent cyclization under mild conditions. In a final alkylation step a further substituent may be introduced. The synthetic strategy allows broad structural variation of this new drug-like heterobicyclic scaffold. In addition to extensive NMR and MS analyses, the structure of one derivative was confirmed by X-ray crystallography.

Synthesis of novel oxindolylpyrrolo[2,3-d]pyrimidines via a three-component sequential tandem reaction

A novel one-pot three-component reaction of 6-amino-uracil, isatin, and acetophenone was accomplished through a programmed pH variation for the synthesis of 5-(2-oxoindolin-3-yl)-1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione derivatives. The reaction was conducted in a sequential tandem manner to give the oxindole substituted pyrrolo[2,3-d]pyrimidine products in good to excellent yields. Despite of timing all the processes were carried out in one pot. Most of these novel compounds show narrow to good spectrum of antimicrobial activities in vitro.

ChemInform Abstract: Synthesis of 5‐Benzyl‐2‐phenylpyrazolo[1,5‐a]pyrazin‐4,6(5H,7H)‐dione Derivatives and Discovery of an Apoptosis Inducer for H322 Lung Cancer Cells.

AbstractNovel pyrazolo‐fused dihydropyrazine diones (I) are synthesized and tested for their inhibitory effects on the proliferation of A549 and H322 lung cancer cells.

An efficient synthesis of 3-ethoxypyrrolidine-2,5-diones and cis-2,3,3a,6a-tetrahydrofuro[2,3-c]pyrrole-4,6(5H)-diones from β-cyanocarboxylic acids

A simple and convenient procedure for the synthesis of a new series of 3-ethoxypyrrolidine-2,5- diones and cis-2,3,3a,6a-tetrahydrofuro(2,3-c)pyrrole-4,6(5H)-diones derivatives is described. All compounds were obtained from the direct cyclization of two β-cyanocarboxylic acids with primary amines and amino alcohols in short reaction time and good yields.

Synthesis, crystal structure and rearrangements of orthocyclophane cyclotetraveratrylene (CTTV) tetraketone

Oxidation of cyclotetraveratrylene (CTTV) with potassium permanganate in pyridine under reflux gave tetraketone (the [14]ketonand) 3 which exists as a previously unobserved barrel conformation with S4 symmetry in the crystal structure, although the more familiar ‘boat’ conformer was shown by semi-empirical AM1 calculations to be 3.03 kcal/mol lower in energy. In addition to CTTV tetraketone 3, an isomeric bis-spirolactone 4 was isolated from the basic oxidation conditions, analogous to the product of trans-annular attack and rearrangement observed with oxidation of cyclotriveratrylene, whereas in acid at elevated temperatures, tetraketone 3 underwent a very efficient rearrangement and decarboxylation to afford the highly symmetric spirobi[anthracene]-10,10′-dione derivative 5.