- Pd(ii)-Catalyzed [4 + 1 + 1] cycloaddition of simple: O -aminobenzoic acids, CO and amines: Direct and versatile synthesis of diverse N -substituted quinazoline-2,4(1 H,3 H)-diones
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The mild, efficient, and straightforward synthesis of pharmaceutically and biologically active N3-substituted and N1,N3-disubstituted quinazoline-2,4-(1H,3H)-diones from simple and readily available substrates has been a huge challenge. Described here is a Pd(ii)-catalyzed [4 + 1 + 1] modular synthesis of diverse quinazoline-2,4-(1H,3H)-diones through one-pot cascade reactions of cyclocondensation of o-(alkyl)aminobenzoic acids with CO, amidation of the intermediate isatoic anhydrides with amines, and unprecedented carbonylation of the resulting o-aminobenzamides with CO under 1 atm and 60 °C conditions. The chemoselective and versatile multicomponent reaction allows for the diversities of the products including N3-substituted and N1,N3-disubstituted products, and even makes the substituents on N1,N3 the same or different from each other, which cannot be achieved by most traditional synthetic strategies. This journal is
- Ding, Qianqian,Fan, Xuesen,Wang, Jinjun,Yang, Jingyi,Zhang, Guisheng,Zhang, Xiaopeng
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p. 526 - 535
(2021/01/28)
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- Harnessing selective PET and EnT catalysis by chlorophyll to synthesizeN-alkylated quinoline-2(1H)-ones, isoquinoline-1(2H)-ones and 1,2,4-trioxanes
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Photocatalytic syntheses of quinoline-2(1H)-ones, isoquinoline-1(2H)-ones and 1,2,4-trioxanes were achieved by selective photo-induced electron transfer (PET) and energy transfer (EnT), respectively, by chlorophyll under visible light irradiation. Quinoli
- Banu, Saira,Singh, Kuldeep,Tyagi, Shaifali,Yadav, Anjali,Yadav, Prem P.
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supporting information
p. 9433 - 9438
(2021/11/17)
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- Method for synthesizing quinazoline-2, 4 (1H, 3H)-diketone compound
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The invention discloses a method for synthesizing a quinazoline-2, 4 (1H, 3H)-diketone compound, and belongs to the technical field of synthesis of nitrogen-containing heterocyclic compounds. According to the technical scheme, the method is characterized in that an anthranilic acid compound and an amine compound serve as reaction raw materials, CO serves as a carbonylation reagent, Pd (II) servesas a catalyst, KI or KI/AcOH serves as an additive, Cu (OAc) 2 or O2 or Cu (OAc) 2/O2 serves as an oxidizing agent, and the target product quinazoline-2, 4 (1H, 3H)-diketone compound is prepared through a one-pot multi-component reaction. The method has the advantages of simple and easily available raw material, short synthesis route, high atom economy and step economy, mild reaction conditions, diversified product structures, high yield of most target products and the like.
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Paragraph 0022-0028
(2020/12/30)
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- Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides
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DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA repair mechanisms; however, the lack of potent drug-like inhibitors for use in cellular and in vivo models has limited the investigation of its potential as a novel therapeutic target. Using the crystal structure of human PARG in complex with the weakly active and cytotoxic anthraquinone 8a, novel quinazolinedione sulfonamides PARG inhibitors have been identified by means of structure-based virtual screening and library design. 1-Oxetan-3-ylmethyl derivatives 33d and 35d were selected for preliminary investigations in vivo. X-ray crystal structures help rationalize the observed structure-activity relationships of these novel inhibitors.
- Waszkowycz, Bohdan,Smith, Kate M.,McGonagle, Alison E.,Jordan, Allan M.,Acton, Ben,Fairweather, Emma E.,Griffiths, Louise A.,Hamilton, Niall M.,Hamilton, Nicola S.,Hitchin, James R.,Hutton, Colin P.,James, Dominic I.,Jones, Clifford D.,Jones, Stuart,Mould, Daniel P.,Small, Helen F.,Stowell, Alexandra I. J.,Tucker, Julie A.,Waddell, Ian D.,Ogilvie, Donald J.
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p. 10767 - 10792
(2019/01/04)
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- Synthesis and characterization of the first inhibitor of: N -acylphosphatidylethanolamine phospholipase D (NAPE-PLD)
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N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is a membrane-associated zinc enzyme that catalyzes the hydrolysis of N-acylphosphatidylethanolamines (NAPEs) into fatty acid ethanolamides (FAEs). Here, we describe the identification of the first small-molecule NAPE-PLD inhibitor, the quinazoline sulfonamide derivative 2,4-dioxo-N-[4-(4-pyridyl)phenyl]-1H-quinazoline-6-sulfonamide, ARN19874.
- Castellani, Beatrice,Diamanti, Eleonora,Pizzirani, Daniela,Tardia, Piero,Maccesi, Martina,Realini, Natalia,Magotti, Paola,Garau, Gianpiero,Bakkum, Thomas,Rivara, Silvia,Mor, Marco,Piomelli, Daniele
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supporting information
p. 12814 - 12817
(2017/12/06)
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- 2,4-DIOXO-QUINAZOLINE-6-SULFONAMIDE DERIVATIVES AS INHIBITORS OF PARG
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The present invention relates to compounds of formula I that function as inhibitors of PARG (Poly ADP-ribose glycohydrolase) enzyme activity wherein R1a, R1b, R1c, R1d, R1e, W, X1, X2, X3, X4, X5, X6, X7, c are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which PARG activity is implicated.
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Paragraph 00188; 00189
(2016/07/05)
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- Studies of the H-D exchange mechanism of malonganenone B
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Malonganenone B (1) exhibits an unusual H-D exchange of a formyl proton when in deuteric-NMR solvents. Synthetic and kinetic investigations were made to probe the mechanism of this exchange, which appears to occur via an uncommon and transient amine-amide
- Clark, Peter G. K.,Lein, Matthias,Keyzers, Robert A.
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p. 1725 - 1729
(2012/04/11)
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- Tandem palladium-catalyzed urea arylation-intramolecular ester amidation: Regioselective synthesis of 3-alkylated 2,4-quinazolinediones
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(Chemical Equation Presented) o-Halo benzoates can be combined with monoalkyl ureas in a tandem palladium-catalyzed arylation-ester amidation sequence to deliver quinazolinedione products. The reactions are regioselective for formation of the 3-N-alkyl isomers. Significant variation of both coupling partners is possible, allowing the synthesis of a diverse array of substituted quinazolinediones, exemplified by the preparation of a simple unsymmetric-dialkylated natural product.
- Willis, Michael C.,Snell, Robert H.,Fletcher, Anthony J.,Woodward, Robert L.
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p. 5089 - 5091
(2007/10/03)
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- Synthesis of 5,6-bis(alkyn-1-yl)pyrimidines and related nucleosides
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Sonogashira coupling of 5-iodo-1-methyluracil or 5'-O-TBDMS-5-iodo-2',3'-O-isopropylideneuridine with alkynes gave 5-(alkyn-1-yl) derivatives that underwent 6-lithiation/iodination to give 5-(alkyn-1-yl)-6-iodo-(1-methyluracil or uridine) intermediates (57-80%). Coupling of the 5-(alkyn-1-yl)-6-iodo intermediates gave 5,6-bis(alkyn-1-yl)pyrimidines and protected nucleosides (51-79%). Two of the 5,6-bis(ethynyl)-1,3-dimethyluracil derivatives underwent Bergman cycloaromatization at 130°C with half-lives of 2-8 h. (C) 2000 Published by Elsevier Science Ltd.
- Kumarasinghe,Peterson,Robins
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p. 8741 - 8745
(2007/10/03)
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- Tautomer-dependent Bergman cyclization of novel uracil-enediyne chimeras
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Uracil-enediyne chimeras 4, 7, and 8 were prepared and examined for their propensity to undergo Bergman cyclization. Kinetic experiments showed lactam tautomers 7 and 8 reacted up to 25 times faster than lactim ether 4. Determination of the activation ene
- Kim, Chang-Sik,Diez, Christian,Russell, Keith C.
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p. 1555 - 1558
(2007/10/03)
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- A Mass Spectral Rearrangement of 2-(Alkylamino)benzoic Acid Derivatives and Related Heterocyclic Systems
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The behavior of a series of 2-(alkylamino)benzoic acid derivatives and related heterocyclic systems has been investigated using electron impact mass spectrometry and fragmentation pathways have been formulated.Deuterium-labeled and 13C-labeled compounds w
- Barbuch, Robert J.,Peet, Norton P.
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p. 816 - 820
(2007/10/02)
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- HETEROCYCLIZATION WITH IMINIUM CHLORIDES, III. SYNTHESIS OF 3,4-DIHYDRO-(1H)-1,3,4-BENZOTRIAZEPINE-2,5-DIONES
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A new route to the title compounds has been developed. 3,4-Dihydro-3-methyl-(1H)-1,3,4-benzotriazepine-2,5-dione was prepared by treating 2-dimethylammonio-(4H)-3,1-benzoxazine-4-one chloride with methylhydrazine and cyclizing the 2-dimethylcarbamoylanthr
- Bitter, I.,Szoecs, L.,Toeke, L.
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p. 171 - 180
(2007/10/02)
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- Alkylation des pyrimidines en catalyse par transfert de phase
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Nous rapportons ici, la premiere etude concernant l'alkylation simple et efficace, en catalyse par transfert de phase, de dianions pyrimidiques ambidents derives de l'uracile, de la thymine, du nitro-5 uracile, du fluoro-5 uracile, du chloro-6 uracile, de la tetrahydro-1,2,3,4 dioxo-2,4 quinazoline, conduisant selectivement et avec de hauts rendements, aux derives N1,N3-dialkyles correspondants.
- Hedayatullah, Mir
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p. 339 - 342
(2007/10/02)
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- A Novel Oxamide Rearrangement
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An efficient, base-induced rearrangement of 2-benzoic acid methyl ester (7a) to the isomeric 2-benzoic acid methyl ester (27a) is described.This novel rearrangement must proceed through a spiro intermediate wherein benzoate is acting as a Michael receptor.When 2-benzoic acid methyl ester (28) - an oxamide which would produce a degenerate spiro intermediate - was subjected to rearrangement conditions, the product obtained was 1,3-dimethyl-2,4-(1H,3H)quinazolinedione (29).This latter transformation may have proceeded via a benzodiazepinetrione intermediate.
- Peet, Norton P.,Sunder, Shyam,Barbuch, Robert J.
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p. 1513 - 1518
(2007/10/02)
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