- Synthesis of C-xylopyranosyl- and xylopyranosylidene-spiro-heterocycles as potential inhibitors of glycogen phosphorylase
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New derivatives of d-xylose with aglycons of the most efficient glucose derived inhibitors of glycogen phosphorylase were synthesized to explore the specificity of the enzyme towards the structure of the sugar part of the molecules. Thus, 2-(β-d-xylopyran
- Somsák, László,Bokor, éva,Czibere, Beáta,Czifrák, Katalin,Koppány, Csenge,Kulcsár, László,Kun, Sándor,Szilágyi, Eniko,Tóth, Marietta,Docsa, Tibor,Gergely, Pál
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Read Online
- Hydrogenation of Secondary Amides using Phosphane Oxide and Frustrated Lewis Pair Catalysis
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The metal-free catalytic hydrogenation of secondary carboxylic acid amides is developed. The reduction is realized by two new catalytic reactions. First, the amide is converted into the imidoyl chloride by triphosgene (CO(OCCl3)2) using novel phosphorus(V) catalysts. Second, the in situ generated imidoyl chlorides are hydrogenated in high yields by an FLP-catalyst. Mechanistic and quantum mechanical calculations support an autoinduced catalytic cycle for the hydrogenation with chloride acting as unusual Lewis base for FLP-mediated H2-activation.
- K?ring, Laura,Sitte, Nikolai A.,Bursch, Markus,Grimme, Stefan,Paradies, Jan
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supporting information
p. 14179 - 14183
(2021/09/03)
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- Transition Metal-Free Visible Light-Driven Photoredox Oxidative Annulation of Arylamidines
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A fast catalytic synthesis of multisubstituted quinazolines from readily available amidines via visible light-mediated oxidative C(sp3)-C(sp2) bond formation has been established. This reaction is a metal-free oxidative coupling catalyzed by a photoredox organocatalyst. The protocol features low catalyst loading (1 mol %).
- Shen, Zi-Chao,Yang, Pan,Tang, Yu
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p. 309 - 317
(2016/01/15)
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- Synthesis of Quinazolines from N,N′-Disubstituted Amidines via I2/KI-Mediated Oxidative C-C Bond Formation
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An I2/KI-promoted oxidative C-C bond formation reaction from C(sp3)-H and C(sp2)-H bonds has been used to construct quinazoline skeletons from N,N′-disubstituted amidines. The required substrates are readily prepared from the corresponding acyl chlorides, anilines, and alkyl/benzylamines by sequential amidation, chlorination, and amination reactions. Under the optimal oxidative cyclization conditions, all these amidines were conveniently transformed into the expected products in moderate to good yields. This practical and environmentally benign approach works well with crude amidine intermediates and can also be carried out on a gram scale.
- Lv, Zhigang,Wang, Bingnan,Hu, Zhiyuan,Zhou, Yiming,Yu, Wenquan,Chang, Junbiao
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supporting information
p. 9924 - 9930
(2016/11/02)
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- Computationally motivated synthesis and enzyme kinetic evaluation of N-(β-d-glucopyranosyl)-1,2,4-triazolecarboxamides as glycogen phosphorylase inhibitors
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Following our recent study of N-(β-d-glucopyranosyl)oxadiazolecarboxamides (Polyk et al., Biorg. Med. Chem. 2013, 21, 5738) revealed as moderate inhibitors of glycogen phosphorylase (GP), in silico docking calculations using Glide have been performed on N-(β-d-glucopyranosyl)-1,2,4-triazolecarboxamides with different aryl substituents predicting more favorable binding at GP. The ligands were subsequently synthesized in moderate yields using N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-tetrazole-5-carboxamide as starting material. Kinetics experiments against rabbit muscle glycogen phosphorylase b (RMGPb) revealed the ligands to be low μM GP inhibitors; the phenyl analogue (Ki = 1 μM) is one of the most potent N-(β-d-glucopyranosyl)-heteroaryl-carboxamide-type inhibitors of the GP catalytic site discovered to date. Based on QM and QM/MM calculations, the potency of the ligands is predicted to arise from favorable intra- and intermolecular hydrogen bonds formed by the most stable solution phase tautomeric (t2) state of the 1,2,4-triazole in a conformationally dynamic system. ADMET property predictions revealed the compounds to have promising pharmacokinetic properties without any toxicity. This study highlights the benefits of a computationally led approach to GP inhibitor design. This journal is
- Begum, Jaida,Varga, Gergely,Docsa, Tibor,Gergely, Pl,Hayes, Joseph M.,Juhsz, Lszl,Somsk, Lszl
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supporting information
p. 80 - 89
(2015/02/02)
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- Semi-catalytic reduction of secondary amides to imines and aldehydes
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Secondary amides can be reduced by silane HSiMe2Ph into imines and aldehydes by a two-stage process involving prior conversion of amides into iminoyl chlorides followed by catalytic reduction mediated by the ruthenium complex [Cp(i-Pr3P)Ru(NCCH3)2]PF6 (1). Alkyl and aryl amides bearing halogen, ketone, and ester groups were converted with moderate to good yields under mild reaction conditions to the corresponding imines and aldehydes. This procedure does not work for substrates bearing the nitro-group and fails for heteroaromatic amides. In the case of cyano substituted amides, the cyano group is reduced to imine.
- Lee, Sun-Hwa,Nikonov, Georgii I.
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supporting information
p. 8888 - 8893
(2014/06/09)
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- METHOD FOR THE CATALYTIC REDUCTION OF ACID CHLORIDES AND IMIDOYL CHLORIDES
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The present application relates to methods for the catalytic reduction of acid chlorides and/or imidoyl chlorides. The methods comprise reacting the acid chloride or imidoyl chloride with a silane reducing agent in the presence of a catalyst such as [Cp(Pri3P)Ru(NCMe)2]+[PF6]?.
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Paragraph 0117; 0118
(2014/08/19)
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- New synthesis of 3-(β-D-glucopyranosyl)-5-substituted-1,2,4-triazoles, nanomolar inhibitors of glycogen phosphorylase
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O-Perbenzoylated 5-(β-D-glucopyranosyl)tetrazole was reacted with N-benzyl carboximidoyl chlorides to give the corresponding 4-benzyl-3-(β-D- glucopyranosyl)-5-substituted-1,2,4-triazoles. Removal of the O-benzoyl and N-benzyl protecting groups by base catalysed transesterification and catalytic hydrogenation, respectively, furnished a series of 3-(β-D-glucopyranosyl)- 5-substituted-1,2,4-triazoles with aliphatic, mono- and bicyclic aromatic, and heterocyclic substituents in the 5-position. Enzyme kinetic studies revealed these compounds to inhibit rabbit muscle glycogen phosphorylase b: best inhibitors were the 5-(4-aminophenyl)- (Ki 0.67 μM) and the 5-(2-naphthyl)-substituted (Ki 0.41 μM) derivatives. This study uncovered the C-glucopyranosyl-1,2,4-triazoles as a novel skeleton for nanomolar inhibition of glycogen phosphorylase.
- Kun, Sándor,Bokor, éva,Varga, Gergely,Szocs, Béla,Páhi, András,Czifrák, Katalin,Tóth, Marietta,Juhász, László,Docsa, Tibor,Gergely, Pál,Somsák, László
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p. 567 - 579
(2014/04/03)
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- Solvent/oxidant-switchable synthesis of multisubstituted quinazolines and benzimidazoles via metal-free selective oxidative annulation of arylamidines
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A fast and simple divergent synthesis of multisubstituted quinazolines and benzimidazoles was developed from readily available amidines, via iodine(III)-promoted oxidative C(sp3)-C(sp2) and C(sp 2)-N bond formation in nonpolar and polar solvents, respectively. Further selective synthesis of quinazolines in polar solvent was realized by TEMPO-catalyzed sp3C-H/sp2C-H direct coupling of the amidine with K2S2O8 as the oxidant. No metal, base, or other additives were needed.
- Lin, Jian-Ping,Zhang, Feng-Hua,Long, Ya-Qiu
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supporting information
p. 2822 - 2825
(2014/06/23)
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- Metal-free aminoamidiniumation employing N-iodosuccinimide: Facile syntheses of bicyclic imidazolidiniums and cyclic vicinal diamines
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NIS-mediated aminoamidiniumation has been developed for the syntheses of bicyclic imidazolidinium salts, which could be readily converted into cyclic vicinal diamines.
- Zhang, Jun,Zhang, Gengtao,Wu, Weijie,Zhang, Xuejun,Shi, Min
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supporting information
p. 15052 - 15054
(2014/12/11)
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- Transition metal-free one-pot synthesis of 2-substituted 3-carboxy-4-quinolone and chromone derivatives
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A novel one-pot synthesis of the 2-substituted 3-carboxy-4-quinolone/ chromone derivatives from readily available 3-oxo-3-arylpropanoates and amides/acyl chlorides is reported, without any transition metal aid. The Royal Society of Chemistry 2013.
- Lin, Jian-Ping,Long, Ya-Qiu
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supporting information
p. 5313 - 5315
(2013/06/27)
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- GLYCOGEN PHOSPHORYLASE INHIBITORS
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The invention relates to compounds of formula (I) and stereoisomers, tautomers and pharmaceutically acceptable salts thereof and processes for preparing them. In formula (I) X is -CH= or -N= or -N(R") -; Y is -N= or -N(R") -; R is an alkyl group, an aryl group or a heteroaryl group, which groups are unsubstituted or substituted; R' is hydrogen or PG1, R" is hydrogen or PG2, R"' is hydrogen or R'OCH2-; n is an integer of 1 to 3. The invention also relates to pharmaceutical compositions containing these compounds. The compounds according to the invention are glycogen phosphorylase inhibitors and can be used e.g. for the treatment of type 2 diabetes, cardiovascular disorders and tumorous growth.˙
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Page/Page column 25
(2013/05/21)
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- Parallel copper catalysis: Diastereoselective synthesis of polyfunctionalized azetidin-2-imines
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An efficient and diastereoselective synthesis of highly functionalized azetidin-2-imines has been achieved through a parallel catalysis strategy, including a copper-catalyzed azide-alkyne cycloaddition, a copper-catalyzed Csp-Csp2 cr
- Xing, Yanpeng,Zhao, Hongyang,Shang, Qiongyi,Wang, Jing,Lu, Ping,Wang, Yanguang
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supporting information
p. 2668 - 2671
(2013/07/19)
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- 5-Imino-1,2,4-thiadiazoles: First small molecules As substrate competitive inhibitors of glycogen synthase kinase 3
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Cumulative evidence strongly supports that glycogen synthase kinase-3 (GSK-3) is a pathogenic molecule when it is up-dysregulated, emerging as an important therapeutic target in severe unmet human diseases. GSK-3 specific inhibitors might be promising effective drugs for the treatment of devastating pathologies such as neurodegenerative diseases, stroke, and mood disorders. As GSK-3 has the ability to phosphorylate primed substrates, small molecules able to bind to this site should be perfect drug candidates, able to partially block the activity of the enzyme over some specific substrates. Here, we report substituted 5-imino-1,2,4-thiadiazoles as the first small molecules able to inhibit GSK-3 in a substrate competitive manner. These compounds are cell permeable, able to decrease inflammatory activation and to selectively differentiate neural stem cells. Overall, 5-imino-1,2,4-thiadiazoles are presented here as new molecules able to decrease neuronal cell death and to increase endogenous neurogenesis blocking the GSK-3 substrate site
- Palomo, Valle,Perez, Daniel I.,Perez, Concepcion,Morales-Garcia, Jose A.,Soteras, Ignacio,Alonso-Gil, Sandra,Encinas, Arantxa,Castro, Ana,Campillo, Nuria E.,Perez-Castillo, Ana,Gil, Carmen,Martinez, Ana
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experimental part
p. 1645 - 1661
(2012/04/04)
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- Tandem synthesis of 1-(alkylamino)-2,4-diarylpyrimido[6,1-a]isoquinolin-5-ium chlorides from isoquinoline, N-alkyl-benzimidoyl chlorides, and isocyanides
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1-(Alkylamino)-2,4-diarylpyrimido[6,1-a]isoquinolin-5-ium chlorides are obtained in good yields via a tandem reaction between isoquinoline, N-alkyl-benzimidoyl chlorides and alkyl isocyanides in anhydrous acetonitrile.
- Yavari, Issa,Khalili, Gholamhossein,Mirzaei, Anvar
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experimental part
p. 1190 - 1192
(2010/04/23)
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- Nitrile Ylides: Diastereoselective cycloadditions using chiral oxzolidinones without Lewis acid
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"Chemical Equation Presented" Lewis acid complexation Is generally required for chiral-auxiliary-controlled stereoselectivity, and chiral Lewis acid catalysis Is frequently optimal for Introducing asymmetry. In this work, we show that nitrlle ylide cycloadditions to electron-poor acceptors attached to chiral auxiliaries proceed In high yield and stereoselectivity in the absence of Lewis acids. In contrast, chiral Lewis acids are Inferior In these cycloadditions.
- Mukund P, Sibi,Soeta, Takahlro,Jasperse, Craig P.
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supporting information; experimental part
p. 5366 - 5369
(2010/02/28)
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- Convenient synthesis of 2-alkylamino-6-carboxy-5,7-diarylcyclopenteno[1,2- b]pyridines via direct acylamination with imidoyl chlorides
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A robust synthetic method for 2-alkylamino-6-carboxy-5,7- diarylcyclopenteno[1,2-b]pyridines via acylamination at the alpha position of the functionalized pyridine system has been developed. The key step in this method was achieved by treatment of the corresponding pyridine N-oxides with 2.5 equiv of imidoyl chlorides in the presence of triethylamine, thus producing the desired 2-acylaminopyridines in good yields (74-96%).
- Takahashi, Hirobumi,Fukami, Takehiro,Kojima, Hisaki,Yamakawa, Takeru,Takahashi, Hiroyuki,Sakamoto, Toshihiro,Nishimura, Teruyuki,Nakamura, Masayuki,Yosizumi, Takashi,Niiyama, Kenji,Ohtake, Norikazu,Hayama, Takashi
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p. 3473 - 3481
(2007/10/03)
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- A novel synthesis of imidazoles via the cycloaddition of nitrile ylides to their imidoyl chloride precursors
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The synthesis of imidazoles via the cycloaddition of nitrile ylides to their imidoyl chloride precursors was presented. The nitrile ylides were prepared by the 1,3-dehydrochlorination of imidoyl chlorides. It was shown that the HOMO of the 'bent' nitrile ylide is heavily localized on the methane terminus and is compatible with protonation at this carbon in substituted nitrile ylides and with the regioisomers obtained in biomolecular nitrile ylide cycloadditions. The observed regiochemistry of the cycloaddition was rationalized by energy calculations on the frontier molecular orbitals of the reactants using semi-empirical methods.
- Groundwater, Paul W.,Garnett, Ian,Morton, Andrew J.,Sharif, Toqir,Coles, Simon J.,Hursthouse, Michael B.,Nyerges, Miklos,Anderson, Rosaleen J.,Bendell, David,McKillop, Alexander,Zhang, Weimin
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p. 2781 - 2787
(2007/10/03)
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- Kinetics of the Reactions of Phenylchlorocarbene with Alkyl Azides
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The reactions of phenylchlorocarbene with several alkyl azides lead to C-chloroimines (and derived N-alkylbenzamides) with absolute rate constants of ca. 1-4 x 107 M-1 s-1.
- Moss, Robert A.,Jang, Eun G.,Krogh-Jespersen, Karsten
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p. 1409 - 1412
(2007/10/02)
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- OPTISCH AKTIVE UEBERGANGSMETALL-KOMPLEXE. LXVII. KONFORMATIONSANALYSE DER DIASTEREOMEREN-GLEICHGEWICHTE VON QUADRATISCH-PYRAMIDALEN C2H5(CO)2Mo-AMIDINATO-KOMPLEXEN
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C5H5Mo(CO)3Cl and amidines react with formation of C5H5(CO)2Mo-amidinato chelate complexes, in which the Mo atom is an asymmetric center.With optically active amidines pairs of diastereoisomers and with racemic chiral amidines diastereoisomeric pairs of e
- Brunner, Henri,Lukassek, Juergen,Agrifoglio, Giuseppe
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