Their Evaluation (their + evaluation)

Distribution by Scientific Domains


Selected Abstracts


Synthesis of 2-Azabicyclo[3.2.2]nonane-Derived Monosaccharide Mimics and Their Evaluation as Glycosidase Inhibitors

HELVETICA CHIMICA ACTA, Issue 3 2006
Stephan Buser
Abstract The racemic 2-azabicyclo[3.2.2]nonanes 5 and 18 were synthesized and tested as , -glycosidase inhibitors. The intramolecular Diels,Alder reaction of the masked o -benzoquinone generated from 2-(allyloxy)phenol (6) gave the , -keto acetal 7 which was reduced with SmI2 to the hydroxy ketone 8. Dihydroxylation, isopropylidenation (,,12), and Beckmann rearrangement provided lactam 15. N -Benzylation of this lactam, reduction to the amine 17, and deprotection provided the amino triol 19 which was debenzylated to the secondary amine 5. Both 5 and 19 proved weak inhibitors of snail , -mannosidase (IC50,>,10,mM), Caldocellum saccharolyticum , -glucosidase (IC50,>,10,mM), sweet almond , -glucosidase (IC50,>,10,mM), yeast , -glucosidase (5: IC50,>,10,mM; 19: IC50,=,1.2,mM), and Jack bean , -mannosidase (no inhibition detected). [source]


Synthesis of New C(2) -Substituted gluco -Configured Tetrahydroimidazopyridines and Their Evaluation as Glucosidase Inhibitors

HELVETICA CHIMICA ACTA, Issue 10 2005
Bhagavathy Shanmugasundaram
The gluco -configured C(2) -substituted tetrahydroimidazopyridines 8,14 were prepared and tested as inhibitors of the , -glucosidases from Caldocellum saccharolyticum and from sweet almonds, and of the , -glucosidase from brewer's yeast. All new imidazopyridines are nanomolar inhibitors of the , -glucosidases and micromolar inhibitors of the , -glucosidase. The 3-phenylpropyl derivative 14 proved the strongest inhibitor of the Caldocellum , -glucosidase (Ki,=,0.9,nM), only slightly weaker than the known 2-phenylethyl analogue 7, and the propyl derivative 13 is the strongest inhibitor of the sweet almond , -glucosidases (Ki,=,3.2,nM), again slightly weaker than 7. There is no strong dependence of the inhibition on the nature of the C(2) -substituent and no clear correlation between the inhibitory strength of the known manno -configured imidazopyridines 2,6 and the gluco -analogues 8,12. While most manno -imidazopyridines are competitive inhibitors, the gluco -analogues proved non-competitive inhibitors of the Caldocellum , -glucosidase and mixed-type or partial mixed-type inhibitors of the sweet almond , -glucosidases. [source]


Synthesis of N -Acetylglucosamine-Derived Nagstatin Analogues and Their Evaluation as Glycosidase Inhibitors

HELVETICA CHIMICA ACTA, Issue 1 2005
Miroslav Terinek
The gluco -configured analogue 15 of nagstatin (1) and the methyl ester 14 were synthesized via condensation of the thionolactams 17 or 18 with the , -amino ester 19. The silyl ethers 20 and 21 resulting from 17 were desilylated to 22 and 23; these alcohols were directly obtained by condensing 18 and 19. The attempted substitution of the C(8)OH group of 22 by azide under Mitsunobu conditions led unexpectedly to the deoxygenated , -azido esters 24. The desired azide 25 was obtained by treating the manno -configured alcohol 23 with diphenyl phosphorazidate. The azide was transformed to the debenzylated acetamido ester 14 that was hydrolyzed to the nagstatin analogue 15. The imidazole-2-acetates 14 and 15 are nanomolar inhibitors of the N -acetyl- , -glucosaminidases from Jack beans and from bovine kidney, submicromolar to micromolar inhibitors of the , -glucosidase from Caldocellum saccharolyticum, and rather weak inhibitors of the snail , -mannosidase. In all cases, the ester was a stronger inhibitor than the corresponding acid. As expected from their gluco -configuration, both imidazopyridines 14 and 15 are stronger inhibitors of the , - N -acetylglucosaminidase from bovine kidney than nagstatin. [source]


Synthesis of Monosaccharide-Derived Spirocyclic Cyclopropylamines and Their Evaluation as Glycosidase Inhibitors

HELVETICA CHIMICA ACTA, Issue 9 2003
Christian Blüchel
The glucose-, mannose-, and galactose-derived spirocyclic cyclopropylammonium chlorides 1a,1d, 2a,2d and 3a,3d were prepared as potential glycosidase inhibitors. Cyclopropanation of the diazirine 5 with ethyl acrylate led in 71% yield to a 4,:,5,:,1,:,20 mixture of the ethyl cyclopropanecarboxylates 7a,7d, while the Cu-catalysed cycloaddition of ethyl diazoacetate to the exo -glycal 6 afforded 7a,7d (6,:,2,:,5,:,3) in 93,98% yield (Scheme,1). Saponification, Curtius degradation, and subsequent addition of BnOH or t- BuOH led in 60,80% overall yield to the Z- or Boc-carbamates 11a,11d and 12a,12d, respectively. Hydrogenolysis of 11a,11d afforded 1a,1d, while 12a,12d was debenzylated to 13a,13d prior to acidic cleavage of the N -Boc group. The manno - and galacto -isomers 2a,2d and 3a,3d, respectively, were similarly obtained in comparable yields (Schemes,2 and 4). Also prepared were the differentially protected manno- configured esters 24a,24d; they are intermediates for the synthesis of analogous N -acetylglucosamine-derived cyclopropanes (Scheme,3). The cyclopropylammonium chlorides 1a,1d, 2a,2d and 3a,3d are very weak inhibitors of several glycosidases (Tables,1 and 2). Traces of Pd compounds, however, generated upon catalytic debenzylation, proved to be strong inhibitors. PdCl is, indeed, a reversible, micromolar inhibitor for the ,- glucosidases from C. saccharolyticum and sweet almonds (non-competitive), the , -galactosidases from bovine liver and from E. coli (both non-competitive), the , -galactosidase from Aspergillus niger (competitive), and an irreversible inhibitor of the , -glucosidase from yeast and the , -galactosidase from coffee beans. The cyclopropylamines derived from 1a,1d or 3a,3d significantly enhance the inhibition of the ,- glucosidase from C. saccharolyticum by PdCl, lowering the Ki value from 40,,M (PdCl) to 0.5,,M for a 1,:,1 mixture of PdCl and 1d. A similar effect is shown by cyclopropylamine, but not by several other amines. [source]


ChemInform Abstract: A New Facile Synthesis of 3-Amidoindole Derivatives and Their Evaluation as Potential GSK-3, Inhibitors.

CHEMINFORM, Issue 27 2010
Anahit Pews-Davtyan
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]


Parallel Synthesis of a Library of Acylsemicarbazides Using a Solution-Phase One-Pot Method and Their Evaluation as Crop-Protection Agents.

CHEMINFORM, Issue 4 2006
Justyna A. Grzyb
Abstract For Abstract see ChemInform Abstract in Full Text. [source]


Synthesis of Tricyclic Analogues of Stephaoxocanidine and Their Evaluation as Acetylcholinesterase Inhibitors.

CHEMINFORM, Issue 40 2005
Dario A. Bianchi
Abstract For Abstract see ChemInform Abstract in Full Text. [source]


Synthesis of New N-(2-(Trifluoromethyl)pyridin-4-yl)anthranilic Acid Derivatives and Their Evaluation as Anticancer Agents.

CHEMINFORM, Issue 13 2005
Maria T. Cocco
Abstract For Abstract see ChemInform Abstract in Full Text. [source]


Synthesis of 1-Methyl-5-(pyrazol-3- and -5-yl- and 1,2,4-triazol-3- and 5-yl)-1,2,3,6-tetrahydropyridine Derivatives and Their Evaluation as Muscarinic Receptor Ligands.

CHEMINFORM, Issue 39 2003
Maria Rosaria Del Giudice
Abstract For Abstract see ChemInform Abstract in Full Text. [source]