← Back to Search
Synthesis Of Bicyclic N‐Arylmethyl‐Substituted Iminoribitol Derivatives As Selective Nucleoside Hydrolase Inhibitors
M. Berg, G. Bal, A. Goeminne, Pieter Van der Veken, W. Versées, J. Steyaert, Achiel Haemers, K. Augustyns
Published 2009 · Chemistry, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
A series of bicyclic N‐arylmethyl‐substituted iminoribitols were synthesised and evaluated in vitro against T. vivax nucleoside hydrolase. The importance of the N–Asp40 interaction was confirmed and depends on an optimal pKa value, which can be influenced by substituents. The compounds were active inhibitors of nucleoside hydrolase (IAG‐NH) and are inactive against human purine nucleoside phosphorylase.
This paper references
Polyhydroxylated pyrrolidines from sugar lactomes: Synthesis of 1,4-dideoxy-1,4-imino-d-glucitol from d-galactonolactone and syntheses of 1,4-dideoxy-1,4-imino-d-allitol, 1,4-dideoxy-1,4-imino-d-ribitol, and (2s,3r,4s)-3,4-dihydroxyproline from d-gulonolactone
G. Fleet (1988)
min, m/z 296.1 [M+H] + . Keywords: enzymes · inhibitors · metabolism · nucleoside hydrolase · purine salvage pathway · trypanosomiasis  a) World Health Organization (WHO)
Es -Ms (2002)
A new diaza‐18‐crown‐6 ligand containing two quinolin‐8‐ylmethyl side arms: Crystal structures and characterization of the ligand, the protonated ligand and its mononuclear barium(II) and dinuclear copper(II) complexes
N. Dalley (2001)
Potential chemotherapeutic targets in the purine metabolism of parasites.
M. H. Kouni (2003)
Enzyme-Substrate Interactions in the Purine-specific Nucleoside Hydrolase from Trypanosoma vivax*
W. Versées (2002)
HPLC (I, l = 254 nm): t R = 11.7 min (100 %), (I, l = 214 nm): t R = 11.6 min (100 %); 1 H NMR (400 MHz
Transition state analogue inhibitors of protozoan nucleoside hydrolases.
R. Furneaux (1999)
Transition-state complex of the purine-specific nucleoside hydrolase of T. vivax: enzyme conformational changes and implications for catalysis.
W. Versées (2006)
Compound 33 (0.124 g, 0.51 mmol) was used in procedure D. The crude product was purified by flash column chromatography (hexane to hexane/EtOAc 1:1); yield: 0.18 g (78 %). 1 H NMR (400 MHz
Compound 39 (0.30 g, 2.0 mmol) was used in procedure F, and the crude residue was purified by flash column chromatography (SiO 2 , hexane to hexane/EtOAc 1:1); yield: 0.27 g, 30 %. 1 H NMR (400 MHz
Synthesis and biochemical evaluation of guanidino-alkyl-ribitol derivatives as nucleoside hydrolase inhibitors.
A. Goeminne (2008)
07 mmol) was used in procedure C. The pure product was obtained after purification by flash column chromatography (SiO 2 , hexane to hexane/EtOAc
Compound 32 (1.12 g, 6.77 mmol) was used in procedure A
Synthesis and antibacterial activity of new 4-alkoxy, 4-aminoalkyl and 4-alkylthioquinoline derivatives
Marie-Gratia Kayirere (1998)
12 mmol) was used in procedure E, and the crude residue was purified by flash column chromatography (SiO 2 , CH 2 Cl 2 to CH 2 Cl 2 /MeOH, 4:1); yield: 0.042 g (89 %)
g (33 %). 1 H NMR (400 MHz
Studies of the reactions between indole-2,3-diones (isatins) and 2-aminobenzylamine
J. Bergman (2003)
Weinheim www.chemmedchem.org (s, 3 H), 2.89 (dd, J = 10.3 Hz, J' = 2.5 Hz, 1 H)
-Vch Verlag Wiley
b): Compound 27 (0.039 g, 0.088 mmol) was used in procedure E, and the crude residue was purified by flash column chromatography
Improved, high yield synthesis of 3H-quinazolin-4-ones, the key intermediates of recently developed drugs.
László Őrfi (2004)
CDCl 3 ): d = 0.03 (s, 3 H), 0.05 (s, 3 H), 0.87 (s, 9 H), 1.34 (s, 3 H), 1.35 (s, 3 H), 2.88 (dd
N-Arylmethyl substituted iminoribitol derivatives as inhibitors of a purine specific nucleoside hydrolase.
A. Goeminne (2008)
Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis.
A. Fedorov (2001)
HPLC (II, l = 254 nm): t R = 6
Transition-state analysis of nucleoside hydrolase from Crithidia fasciculata.
B. Horenstein (1991)
1,2,3-Triazolylalkylribitol derivatives as nucleoside hydrolase inhibitors.
A. Goeminne (2007)
A Goeminne (2008)
Relationships between the HOMO energies and pKa values in monocyclic and bicyclic azines
H. Machado (1995)
and the residue was purified by flash column chromatography (SiO 2 , hexane to hexane/EtOAc
Synthesis of second-generation transition state analogues of human purine nucleoside phosphorylase.
G. Evans (2003)
87 (s, 2 H)
Structure and function of a novel purine specific nucleoside hydrolase from Trypanosoma vivax.
W. Versées (2001)
Inhibitors of the enzyme purine nucleoside phosphorylase as potential therapy for psoriasis.
P. Morris (2000)
03 (s, 1 H), 9
mmol) was used in procedure E, and the crude residue was purified by flash column chromatography (RPC 18 , H 2 0 to H 2 O/MeCN, 2:8) to give a brown syrup
09 ppm (s, 1 H)
Compound 26 (0.15 g, 0.32 mmol) was used in procedure H, and the crude residue was purified by flash column chromatography (SiO 2 , CH 2 Cl 2 to CH 2 Cl 2 /MeOH, 95:5)
68 mmol) was used in the same procedure as for the synthesis of compound 20; yield: 1.80 g (93 %). 1 H NMR (400 MHz
Iminoribitol transition state analogue inhibitors of protozoan nucleoside hydrolases.
R. W. Miles (1999)
Second generation transition state analogue inhibitors of human 5'-methylthioadenosine phosphorylase.
G. Evans (2005)
A new class of C-nucleoside analogues. 1-(S)-aryl-1,4-dideoxy-1,4-imino-D-ribitols, transition state analogue inhibitors of nucleoside hydrolase
B. Horenstein (1993)
Novel transient receptor potential vanilloid 1 receptor antagonists for the treatment of pain: structure-activity relationships for ureas with quinoline, isoquinoline, quinazoline, phthalazine, quinoxaline, and cinnoline moieties.
A. Gomtsyan (2005)
HPLC (I, l = 254 nm): t R = 5.47 min (100 %), and (I, l = 214 nm): t R = 5.39 min (100 %); 1 H NMR (400 MHz, CD 3 OD): d = 3.52 (s, 1 H), 3.58 (d
36 ppm (s, 2 H)
Nucleoside hydrolase from Crithidia fasciculata. Metabolic role, purification, specificity, and kinetic mechanism.
D. W. Parkin (1991)
Electronic nature of the transition state for nucleoside hydrolase. A blueprint for inhibitor design.
B. Horenstein (1993)
8-Aza-immucillins as transition-state analogue inhibitors of purine nucleoside phosphorylase and nucleoside hydrolases.
G. Evans (2003)
New insights into the mechanism of nucleoside hydrolases from the crystal structure of the Escherichia coli YbeK protein bound to the reaction product.
Laura Muzzolini (2006)
This paper is referenced by
Loop motion and base release in purine-specific nucleoside hydrolase: a molecular dynamics study.
N. Chen (2013)
Novel multi-functional nitrones for treatment of ischemic stroke.
Yewei Sun (2012)
Vrije Universiteit Brussel Structure and mechanism of the 6-oxopurine nucleosidase from Trypanosoma brucei
An Vandemeulebroucke (2010)
Antibacterial activity of quinoxalines, quinazolines, and 1,5-naphthyridines.
Ajit K. Parhi (2013)
Formal Total Synthesis of Diazonamide A
Cheng-Kang Mai (2011)
Evaluation of Nucleoside Hydrolase Inhibitors for Treatment of African Trypanosomiasis
M. Berg (2010)
Unusual O‐Bridged Symmetric Quinoline‐Based Ligand for the Formation of Luminescent Mono‐Aqua Lanthanide Complexes
Hassan Hammoud (2016)
Palladium-catalyzed Z-selective oxidative amination of ortho-substituted primary anilines with olefins under an open air atmosphere.
Yohei Mizuta (2013)
Drug Targets, Drug Effectors, and Drug Targeting and Delivery
P. Loiseau (2013)
QM/MM molecular dynamics study of purine-specific nucleoside hydrolase.
Ruibo Wu (2012)
Evaluation of nucleoside hydrolase inhibitors for the treatment of 1 African trypanosomiasis
Maya Berg (2010)
Crystal structures of T. vivax nucleoside hydrolase in complex with new potent and specific inhibitors.
W. Versées (2009)
Pseudopeptides and Peptidomimetics Modulating the Proteolytic Activity of Kallikrein-related Peptidase 3
Kristian Meinander (2014)
Antileishmanial phytochemical phenolics: molecular docking to potential protein targets.
I. V. Ogungbe (2014)