- Improved synthesis of substituted quinoxalines from new N=N-polymerbound 1,2-diaza-1,3-butadienes
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The first general protocol for the preparation of different N=N-polymer-bound 1,2-diaza-1,3-butadienes is reported. The utility of these supported reagents in the solid-phase in the preparation of 3-methyl quinoxaline-2-carboxylates by reaction with aroma
- Attanasi, Orazio A.,De Crescentini, Lucia,Filippone, Paolino,Mantellini, Fabio,Santeusanio, Stefania
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- Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors
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Herein we report a microscale parallel synthetic approach allowing for rapid access to libraries of N-acylated aminotriazoles and screening of their inhibitory activity against factor XIIa (FXIIa) and thrombin, which are targets for antithrombotic drugs. This approach, in combination with post-screening structure optimization, yielded a potent 7 nM inhibitor of FXIIa and a 25 nM thrombin inhibitor; both compounds showed no inhibition of the other tested serine proteases. Selected N-acylated aminotriazoles exhibited anticoagulant properties in vitro influencing the intrinsic blood coagulation pathway, but not extrinsic coagulation. Mechanistic studies of FXIIa inhibition suggested that synthesized N-acylated aminotriazoles are covalent inhibitors of FXIIa. These synthesized compounds may serve as a promising starting point for the development of novel antithrombotic drugs.
- Platte, Simon,Korff, Marvin,Imberg, Lukas,Balicioglu, Ilker,Erbacher, Catharina,Will, Jonas M.,Daniliuc, Constantin G.,Karst, Uwe,Kalinin, Dmitrii V.
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p. 3672 - 3690
(2021/08/07)
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- Method for synthesizing quinoxaline compounds through double-protein catalytic cascade reaction
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The invention relates to the technical field of biological catalytic synthesis and particularly discloses a method for synthesizing quinoxaline compounds by a double-protein catalytic cascade reaction. The method comprises the steps as follows: a beta-keto ester compound, substituted o-phenylenediamine and methylphenylsulfonyl azido are taken as reactants to be dissolved in a solvent, a catalyst and a surfactant are added, the mixture is stirred to react to produce a product, and the product is sequentially dried, concentrated and purified, wherein the solvent is water, and the catalyst is procine pancreaslipase (PPL) and hemoglobin from bovine blood (HbBv). The process is convenient, a heme protein catalytic carbene reaction and a lipase protein catalytic reaction are coupled to constructa green method for synthesizing quinoxaline compound by double proteins by a one-pot method, the target product can be rapidly and conveniently synthesized, meanwhile, synthesis is completed in water, and the problems that the existing quinoxaline compound preparation method comprises more synthesis steps and is not green and environmentally friendly enough are solved.
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Paragraph 0052-0058
(2021/01/25)
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- A dual-protein cascade reaction for the regioselective synthesis of quinoxalines
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In this work, an efficient dual-protein (lipase and hemoglobin) system was successfully constructed for the regioselective synthesis of quinoxalines in water. A set of quinoxalines were obtained in high yields under optimal reaction conditions. This dual-protein method exhibited a regioselectivity higher than those of previously reported methods. This study not only provides a green and mild strategy for the synthesis of quinoxalines but also expands the application of lipase and hemoglobin in organic synthesis.
- Li, Fengxi,Li, Zhengqiang,Tang, Xuyong,Wang, Chunyu,Wang, Lei,Wang, Zhi,Xu, Yaning
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p. 3900 - 3904
(2020/06/08)
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- Isobutyl Nitrite-Mediated Synthesis of Quinoxalines through Double C?H Bond Amination of N-Aryl Enamines
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An efficient and metal-free double C?H bond amination of N-aryl enamines using isobutyl nitrite (IBN) has been developed. This method enables the preparation of functionalized quinoxalines in good to excellent yields and tolerates a variety of N-aryl enamines with diverse functional substituents. Mechanistic studies revealed the presence of a key β-imino oxime ester intermediate. A quinoxaline derivative could be prepared from β-carbonyl ester in one-pot sequence on a gram scale. Finally, two important quinoxaline scaffolds were easily prepared in moderate yields over two steps. (Figure presented.).
- Jiao, Yan-Xiao,Wei, Lin-Su,Zhao, Chun-Yang,Wei, Kai,Mo, Dong-Liang,Pan, Cheng-Xue,Su, Gui-Fa
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supporting information
p. 4446 - 4451
(2018/10/20)
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- One-Pot Telescoped Synthesis of Thiazole Derivatives from β-Keto Esters and Thioureas Promoted by Tribromoisocyanuric Acid
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A simple and efficient one-pot protocol has been developed for the synthesis of thiazole derivatives from readily available starting materials. Tribromoisocyanuric acid was successfully used for α-monohalogenation of β-keto esters in aqueous medium, which
- De Andrade, Vitor S. C.,De Mattos, Marcio C. S.
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p. 4867 - 4874
(2018/12/13)
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- Tandem C-N Bond Formation through Condensation and Metal-Free N-Arylation: Protocol for Synthesizing Diverse Functionalized Quinoxalines
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Diverse functionalized quinoxalines were synthesized in good yields from arylamines and readily available β-keto oximes through condensation and metal-free N-arylation. The reaction was compatible with various functional groups, such as halides, cyano, and esters. A mechanism was proposed based on the experimental results. These quinoxalines were easily obtained on a gram scale and converted to various useful scaffolds. Compound LASSBio-1022 was prepared in 83% yield in two steps.
- Jiao, Yan-Xiao,Wu, Ling-Ling,Zhu, Hai-Miao,Qin, Jiang-Ke,Pan, Cheng-Xue,Mo, Dong-Liang,Su, Gui-Fa
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p. 4407 - 4414
(2017/04/28)
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- Iron-Catalyzed Annulation of 1,2-Diamines and Diazodicarbonyls for Diverse and Polyfunctionalized Quinoxalines, Pyrazines, and Benzoquinoxalines in Water
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A novel and facile iron-catalyzed tandem annulation of o-phenylenediamines and diazocarbonyls in water for the construction of polyfunctionalized quinoxalines has been developed. The key strategy includes the one-pot domino N?H insertion, cyclization, and
- Pandit, Rameshwar Prasad,Kim, Sung Hong,Lee, Yong Rok
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p. 3586 - 3599
(2016/11/25)
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- 2,3-di-substituted quinoxaline derivatives method for the preparation of
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The invention discloses a novel preparation method for 2,3-disubstituted quinoxaline derivatives. After arylamine and a 1,3-dicarbonyl-2-oxime compound serving as raw materials are condensed, cyclization is performed by using electrophilic substitution reaction of nitrogen positive ions in molecules, so that 'condensation-cyclization' reactions are skillfully linked together, and the 2,3-disubstituted quinoxaline derivatives having different substituent groups on benzene rings are obtained by a two-step one-kettle method. Compared with the traditional synthetic method, the method has the advantages that the raw materials are cheap and readily available; intermediate products do not need to be treated in the process, so that the synthesis steps are simplified; particularly, substitution on the benzene rings can be carried out by using arylamine compounds in many different ways, so that diversity of product structures is realized, and deep study on the quinoxaline derivatives is facilitated. 18 unreported new compounds are also obtained by using the method disclosed by the invention.
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Paragraph 0043; 0044; 0066
(2016/11/24)
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- A rapid synthesis of quinoxalines starting from ketones
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A fast and general synthesis of quinoxalines, performed in two stages or as a one-pot reaction, starting from ketones via their α-hydroxylimino ketone derivatives, and condensation of the latter with 1,2-diaminobenzene under microwave irradiation, is described.
- Padmavathy,Nagendrappa, Gopalpur,Geetha
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p. 544 - 547
(2011/03/18)
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- CeCl3·7H2O-catalyzed synthesis of quinoxaline derivatives in liquid PEG-400
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A mild and efficient route for the synthesis of quinoxaline derivatives utilizing cerium chloride heptahydrate (CeCl3·7H2O) as a novel catalyst in poly(ethylene glycol) (PEG-400) under mild conditions was described.
- Wu, Fang-Wen,Hou, Rei-Sheu,Wang, Huey-Min,Kang, Iou-Jiun,Chen, Ling-Ching
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experimental part
p. 2313 - 2320
(2011/11/06)
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- Quinoxaline synthesis in novel tandem one-pot protocol
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A variety of quinoxalines were synthesized via tandem one-pot procedure for the first time in water medium. The key strategy was the in situ preparation of α-halo-β-keto esters by the reaction of N-bromo succinimide with β-keto esters and further condensa
- Anil Kumar,Madhav,Harsha Vardhan Reddy,Nageswar
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supporting information; experimental part
p. 2862 - 2865
(2011/06/21)
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- TRI-SUBSTITUTED PYRIMIDINE COMPOUNDS AND THEIR USE AS PDE10 INHIBITORS
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The present invention provides a tri-substituted pyrimidine compound having an excellent PDE10 inhibitory activity. The present invention relates to a tri-substituted pyrimidine compound represented by the following formula [I0] or a pharmaceutically acceptable salt thereof, a method for preparing the same, and use of said compound for PDE10 inhibitor, and a pharmaceutical composition comprising said compounds as an active ingredient: wherein: either one of X1 and X2 is N, and the other of X1 and X2 is CH; A is *-CH═CH—, *-C(Alk)=CH—, *-CH2—CH2— or *-O—CH2— (* is a bond with R1); Alk is a lower alkyl group; Ring B is an optionally substituted nitrogen-containing aliphatic heterocyclic group; R1 is an optionally substituted quinoxalinyl or an optionally substituted quinolyl; Y0 is mono- or di-substituted amino group, or a pharmaceutically acceptable salt thereof.
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Page/Page column 22
(2011/07/08)
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- PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS PDE10 INHIBITORS
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The present invention relates to a compound represented by formula [I]: wherein: R1 is hydrogen, halogen, lower alkyl or cyano; Ring A is an optionally substituted heterocyclic group; Ring B is an optionally substituted 3 to 6-membered monocyclic group; and Y is optionally substituted amino, optionally substituted cyclic amino, optionally substituted aliphatic 3 to 6-membered monocyclyloxy, optionally substituted lower alkyl or optionally substituted lower alkyl-O-, or a pharmaceutically acceptable salt thereof, and to their use as PDE10 inhibitor.
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Page/Page column 43-44
(2011/09/30)
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- One-pot synthesis of quinoxaline-2-carboxylate derivatives using ionic liquid as reusable reaction media
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The catalyst-free one-pot synthesis of quinoxaline-2-carboxylate is reported by the reaction of α-halo-β-ketoesters with 1,2-diamines using an ionic liquid as an environmentally benign solvent. The recovered ionic liquid was reused for four to five cycles
- Meshram,Ramesh,Santosh Kumar,Chennakesava Reddy
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experimental part
p. 4313 - 4316
(2010/09/20)
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- AROMATIC NITROGEN-CONTAINING 6-MEMBERED RING COMPOUNDS AND THEIR USE
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The present invention provides aromatic nitrogen-containing 6-membered ring compounds having execellent PDE10 inhibitory activity. The present invention relates to an aromatic nitrogen-containing 6-membered ring compound represented by the following formula [I0] or a pharmaceutically acceptable salt thereof, a method for preparing the same, and use of said compounds for PDE10 inhibitors, and a pharmaceutical composition comprising said compounds as an active ingredient: Formula [I0] wherein: X1, X2 and X3 each independently are N or CH, and at least two of X1, X2 and X3 are N; A is *-CH=CH-, *-C(Alk)=CH-, *-CH2-CH2- or *-O-CH2- (* is a bond with R1); Alk is a lower alkyl group; Ring B is an optionally substituted nitrogen-containing aliphatic heterocyclic group; R1 is an optionally substituted nitrogen-containing heterocyclic group, a nitrogen-containing heterocyclic moiety of which is a moiety selected from the group consisting of quinoxalinyl, quinolyl, isoquinolyl, quinazolinyl, pyrazinyl, pyrimidinyl and a moiety thereof fused with a 5 to 6-membered aliphatic ring thereto; Y0 is a group selected from the group consisting of the following (1) to (5): (1) an optionally substituted phenyl or an optionally substituted aromatic monocyclic 5 to 6-membered heterocyclic group; (2) an optionally substituted aminocarbonyl; (3) an optionally substituted amino lower alkyl; (4) -O-R2 wherein R2 is hydrogen, an optionally substituted lower alkyl, lower cycloalkyl, aliphatic monocyclic 5 to 6-membered heterocyclic group, or Formula [AA]; (5) mono- or di-substituted amino; provided that, when Y0 is mono- or di-substituted amino, the nitrogen-containing heterocyclic moiety of R1 is not quinoxalinyl or quinolyl.
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Page/Page column 58; 59
(2010/04/06)
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- Synthesis of the possible metabolites of quinocetone in animals
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The possible metabolites of quinocetone in animals had been prepared with different selective reagent by three synthetic routes. It was their principal reaction that Na2S2O4 reduced quinoxaline-1,4-dioxide derivatives to quinoxaline derivatives, H 2O2 s oxidized 2-carboxyl-quinoxaline derivatives to 2-carboxyl-quinoxaline-1 -oxide ones and P(OCH3) 3 reduced 2-carboxyl- quinoxaline-1,4-dioxide derivatives to 3-carboxyl-quinoxaline-1-oxide ones. The title compounds ware confirmed with NMR,UV, FAB-MS, et al.
- Li, Jian-Yong,Zhang, Ji-Yu,Zhou, Xu-Zheng,Li, Jin-Shan,Lu, Run-Hua
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- A new convenient liquid- and solid-phase synthesis of quinoxalines from (E)-3-diazenylbut-2-enes
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3-{[(tert-Butoxy)carbonyl]diazenyl} but-2-enoates react in tetrahydrofuran at room temperature with aromatic 1,2-diamines to give 3-methylquinoxaline-2-carboxylates. These products were also obtained in solid-phase synthesis, by using polymer-bound 3-diaz
- Attanasi, Orazio A.,De Crescentini, Lucia,Filippone, Paolino,Mantellini, Fabio,Santeusanio, Stefania
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p. 2379 - 2386
(2007/10/03)
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- Synthesis of 2-oxy> 3-Keto Esters from 3-Keto Esters and (p-Nitrophenyl)sulfonyl Peroxide
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The preparation of 2-oxy> β-keto esters from β-keto esters and (p-nitrophenyl)sulfonyl peroxide is described.High yields are obtained for a variety of structural types.One β-diketone was also used and gave comparable success.Thes
- Hoffman, Robert V.,Wilson, Anna Lee,Kim, Hwa-Ok
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p. 1267 - 1270
(2007/10/02)
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- 2-(((p-Nitrophenyl)sulfonyl)oxy)-3-keto Esters: Versatile Intermediates for the Preparation of 1,2,3-Tricarbonyl Compounds
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The excellent leaving ability of the nosylate group and the high, differentiated functional group density in 2-(((p-nitrophenyl)sulfonyl)oxy)-3-keto esters, 1, suggested that they might serve as versatile precursors for the synthesis of other 1,2,3-trifunctionalized compounds.Reaction of 2-(nosyloxy)-3-keto esters with triethylamine gives 1,2,3-tricarbonyl compounds in high yields.The tricarbonyl compound can be reacted, without isolation, with nucleophiles to give heterocyclic products in excellent yields.
- Hoffman, Robert V.,Kim, Hwa-Ok,Wilson, Anna Lee
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p. 2820 - 2822
(2007/10/02)
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- Deoxygenation of Quinoxaline and Phenazine N-Oxides by Catalytic Transfer Reduction and by Iodide in the Presence of Pyridine/Sulfur Trioxide Complex
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Quinoxaline and phenazine di-N-oxides are deoxygenated under mild conditions by catalytic transfer reduction or by treatment with sodium iodide in the presence of pyridine/sulfur trioxide complex.
- Demirdji, S. H.,Haddadin, M. J.,Issidorides, C. H.
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p. 1735 - 1737
(2007/10/02)
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- REACTION OF o-PHENYLENEDIAMINE WITH ACETOACETIC AND α-CHLOROACETOACETIC ESTERS
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The reactivities of acetoacetic and α-chloroacetoacetic esters in the reaction with o-phenylenediamine are compared.In contrast to the available data, it was established that in polyphosphoric acid(PPA) acetoacetic esters is converted to 4-methyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one and ethyl 3-(2-aminoanilino)-crotonate, while chloroacetoacetic esters is converted to 2-methylbenzimidazole.At 20 deg C chloroacetoacetic esters is converted to ethyl 2-chloro-3-(2-amino-anilino)crotonate.The conversion of this ester to 2-methyl-3-ethoxy-2,3-dihydro-1H-1,5-benzodiazepin-2-one was studied.
- Sheremet, V.I.,Dryuk, V. G.,Solomko, Z. F.,Kremlev, M. M.
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p. 941 - 945
(2007/10/02)
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