4014-90-8Relevant academic research and scientific papers
Chemoenzymatic synthesis of cytokinins from nucleosides: Ribose as a blocking group
Oslovsky, Vladimir E.,Solyev, Pavel N.,Polyakov, Konstantin M.,Alexeev, Cyril S.,Mikhailov, Sergey N.
, p. 2156 - 2163 (2018/03/26)
Nucleoside phosphorylases are involved in the salvage pathways of nucleoside biosynthesis and catalyze the reversible reaction of a nucleobase with α-d-ribose-1-phosphate to yield a corresponding nucleoside and an inorganic phosphate. The equilibrium of these reactions is shifted towards nucleosides, especially in the case of purines. Purine nucleoside phosphorylase (PNP, EC 2.4.2.1) is widely used in labs and industry for the synthesis of nucleosides of practical importance. Bacterial PNPs have relatively broad substrate specificity utilizing a wide range of purines with different substituents to form the corresponding nucleosides. To shift the reaction in the opposite direction we have used arsenolysis instead of phosphorolysis. This reaction is irreversible due to the hydrolysis of the resulting α-d-ribose-1-arsenate. As a result, heterocyclic bases are formed in quantitative yields and can be easily isolated. We have developed a novel method for the preparation of cytokinins based on the enzymatic cleavage of the N-glycosidic bond of N6-substituted adenosines in the presence of PNP and Na2HAsO4. According to the HPLC analysis the conversion proceeds in quantitative yields. In the proposed strategy the ribose residue acts as a protective group. No contamination of the final products with AsO43- has been detected via HPLC-HRMS; simple analytical arsenate detection via ESI-MS has been proposed.
Application of five-membered heterocycle pyrimidine compound
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Paragraph 0077; 0078; 0079; 0080; 0081; 0083; 0084, (2018/09/12)
The invention belongs to the field of medicine and particularly relates to application of a five-membered heterocycle pyrimidine compound with the structural features as shown in formula (I) and the pharmaceutically acceptable salt of the five-membered heterocycle pyrimidine compound serving as nucleotide oxidative damage repairase MTH1 inhibitors. Pharmacological experiment results show that thecompound can evidently inhibit the activity of MTH1 and can be used for preventing and treating clinical diseases related to MTH1.
IMAGING AGENTS FOR NEURAL FLUX
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Page/Page column 123, (2016/02/10)
Provided herein are radiolabeled compounds useful for non-invasive imaging techniques. An exemplary radiolabeled compound provided herein is useful as a radiotracer for positron emission tomography. The present application also provides unlabeled compounds useful in methods of treating diseases of the central nervous system or disease of the peripheral nervous system. Methods for preparing radiolabeled compounds, preparing unlabeled compounds, and diagnostic methods using labeled or unlabeled compounds are also provided.
Method for treating disease or condition susceptible to amelioration by AMPK activators and compounds of formula which are useful to activate AMP-activated protein kinase (AMPK)
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Paragraph 0049-0050, (2014/10/16)
The present invention relates to a method for treating disease or condition susceptible to amelioration by AMPK activators and compounds of formula which are useful to activate AMP-activated protein kinase (AMPK) and the use of the compounds in the prevention or treatment of disease, including pre-diabetes, type 2 diabetes, syndrome X, metabolic syndrome and obesity.
Design, synthesis and preliminary biological evaluation of purine-2,6-diamine derivatives as cyclin-dependent kinase (CDK) inhibitors
Wang, Junhua,Wang, Quande,Zhang, Liangren,Fang, Hao
, p. 1181 - 1191 (2013/10/21)
Novel purine-2,6-diamine derivatives were designed and synthesized as cyclin-dependent kinase (CDK) inhibitors. According to the preliminary biological evaluation, most of the compounds show good inhibitory activities in CDK1 enzyme assay and potent antiproliferative activities in some tumor cell lines. Especially, compound 11a (IC50=0.35 μmol/L for CDK1/cyclin B and IC50=0.023 μmol/L for CDK2/cyclin A) possessed better inhibitory effect compared with Roscovitine (IC50=2.54 (mol/L for CDK1/cyclin B and IC50=0.092 μmol/L for CDK2/cyclin A). Copyright
An efficient synthesis of substituted cytosines and purines under focused microwave irradiation
Huang, Ling-Kuen,Cherng, Yen-Chih,Cheng, Yann-Ru,Jang, Jing-Pei,Chao, Yi-Ling,Cherng, Yie-Jia
, p. 5323 - 5327 (2008/02/01)
A rapid nucleophilic displacement reaction of 6-chloropurine, 2-amino-6-chloropurine and 5-bromocytosine with various nucleophiles under focused microwave irradiation is described. Using this method, the desired products were obtained with the yields up to 99% in?a?short reaction time.
In vitro biotransformation of 2,6,9-trisubstituted purine-derived cyclin-dependent kinase inhibitor bohemine by mouse liver microsomes
Rypka,Vesely,Chmela,Riegrova,Cervenkova,Havliek,Lemr,Hanus,Cerny,Lukes,Michalikova
, p. 1017 - 1031 (2007/10/03)
1. Biotransformation pathways of the cyclin-dependent kinase inhibitor 6-benzylamino-2-(3-hydroxypropylamino)-9-isopropylpurine (bohemine) by mouse liver microsomes in vitro were investigated. 2. Metabolite profiles of [8-3H]-labelled bohemine were established by TLC/3H-autoradiography and enzymatic and MS analyses were used to elucidate the chemical structures of the metabolites. The structures of the main primary metabolites were confirmed by synthesis of authentic compounds. 3. A schema of the primary NADPH-dependent pathways has been proposed involving N2- and N9-dealkylation, N6-debenzylation, aromatic hydroxylation, and C2 side chain oxidation of bohemine. Three of the primary metabolites detected, 6-(benzylamino)-2-(3-hydroxypropylamino)purine (M4), 6-amino-2-(3-hydroxypropylamino)-9-isopropylpurine (M5) and 6-(4-hydroxybenzylamino)-2-(3-hydroxypropylamino)-9-isopropylpurine (M6), all retaining their parent primary hydroxyl group, were subsequently shown to be converted, by a liver cytosolic NAD+-dependent system, into their corresponding carboxylic acids. M6 was subject to microsomal glycosidations requiring UDP-sugar donors. NADPH-dependent conversion of M6 into M5 by microsomes was also demonstrated. 4. Cytochrome P450 (CYP) enzymes-selective inhibitors were used to identify CYPs involved in bohemine biotransformation. The findings suggested that CYP2a and CYP3a substantially contributed to the NADPH-dependent bohemine transformation in vitro. 5. The findings will facilitate experiments designed to dissect enzymatic systems catalysing clearance of C2,C6,N9-trisubstituted purine compounds from mammalian tissues.
Cytokinin-derived cyclin-dependent kinase inhibitors: Synthesis and cdc2 inhibitory activity of olomoucine and related compounds
Havlí?ek, Libor,Hanu?, Jan,Vesely, Jaroslav,Leclerc, Sophie,Meijer, Laurent,Shaw, Gordon,Strnad, Miroslav
, p. 408 - 412 (2007/10/03)
Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of edk inhibition showed that the 1, 3, and 7 positions of the purine ring must remain free, probably for a direct interaction, in which it behaves as a hydrogen bond acceptor. Olomoucine (6-(benzylamino)-2-[(2-hydroxyethyl)amino]-9-methylpurine, OC), roscovitine (6-(benzylamino)2(R)-[[1-(hydroxymethyl)propyl]amino]-9- isopropylpurine), and other N6,2,9-trisubstituted adenines were found to exert a strong inhibitory effect on the p34(cdc2)/cyclin B kinase. Removal or change of the side chain at position 2 or the hydrophobic group at position 9 dramatically decreased the inhibitory activity of olomoucine or roscovitine. Inhibition of cdk with OC and related compounds clearly arrests cell proliferation of many tumor cell lines at G1/S and G2/M transitions and also triggers apoptosis in the target tumor cells in vitro and in vivo. Thus, from a pharmacological point of view, OC may represent a model compound for a new class of antimitotic and antitumor drugs.
