14631-20-0Relevant articles and documents
Synthesis, physicochemical characteristics, and biocompatibility of self-assemble polymers bearing guanine, cytosine, uracil, and thymine moieties
Kim, Jin Chul,Kim, Mihee,Jung, Jungwoon,Lee, Jinseok,Ree, Brian J.,Kim, Heesoo,Kim, Ik Jung,Kim, Jung Ran,Ree, Moonhor
, p. 1151 - 1160 (2015)
We synthesized chemically well-defined brush (i.e., comb-like) polymers bearing guanine, cytosine, uracil, or thymine moieties at the bristle ends. The polymers were stable up to 220 °C and were readily solution-processable, yielding high-quality films. Interestingly, the brush polymers favorably self-assembled to form molecular multibilayer structures stabilized by hydrogen bonding interactions among the nucleobase moieties at the bristle ends, which provided nucleobase-rich surfaces. The multibilayer-structured polymer films showed high water affinity. They also displayed selective protein adsorption, suppressed bacterial adherence, facilitated cell adhesion, and exhibited good biocompatibility in mice. The brush polymer DNA-mimicking comb-like polymers are suitable as biomaterials and in protein separation applications.
Synthesis of N4-β-D-glycoside cytosines and sugar N 4-acetylcytosin-1-ylmethylhydrazones as antiviral agents
Ali, Omar M.,Amer, Hamada H.,Abdel-Rahman, Adel A.-H.
, p. 281 - 283 (2007)
Reaction of monosaccharide aldoses with cytosine (1) gave stereoselectively β-N-glycosides 2a-d, which were treated with acetic anhydride in pyridine to afford the corresponding acetylated derivatives 3a-d. N4- Acetylcytosine (4) was synthesised and treated with ethyl chloroacetatete give 1-(ethoxycarbonylmethy)-N4-acetylcytosine (5). Hydrolysis of the latter ester with hydrazine hydrate afforded the hydrazide derivative 6. Condensation of the hydrazide with monosaccharide aldoses gave the corresponding sugar hydrazones 7a-f. Acetylation of the hydrazones afforded the per-O-acetyl derivatives 8a-f. The prepared compounds were tested for antiviral activity against hepatitis B virus (HBV) which showed moderate activities.
Discovery of α-aminoazaheterocycle-methylglyoxal adducts as a new class of high-affinity inhibitors of cystic fibrosis transmembrane conductance regulator chloride channels
Routaboul, Christel,Norez, Caroline,Melin, Patricia,Molina, Marie-Carmen,Boucherle, Benjamin,Bossard, Florian,Noel, Sabrina,Robert, Renaud,Gauthier, Chantal,Becq, Frederic,Decout, Jean-Luc
, p. 1023 - 1035 (2007)
The cystic fibrosis transmembrane conductance regulator (CFTR) represents the main Cl- channel in the apical membrane of epithelial cells for cAMP-dependent Cl- secretion. Here we report on the synthesis and screening of a small library of nontoxic α-aminoazaheterocycle- methylglyoxal adducts, inhibitors of wild-type (WT) CFTR and G551D-, G1349D-, and F508del-CFTR Cl- channels. In whole-cell patch-clamp experiments of Chinese hamster ovary (CHO) cells expressing WT-CFTR, we recorded rapid and reversible inhibition of forskolin-activated CFTR currents in the presence of the adducts 5a and 8a,b at 10 pM concentrations. Using iodide efflux experiments, we compared concentration-dependent inhibition of CFTR with glibenclamide (IC50 = 14.7 μM), 3-[(3-trifluoromethyl)phenyl]-5- [(4-carboxyphenyl-)methylene]-2-thioxo-4-thiazolidinone (CFTRinh-172) (IC50 = 1.2 μM), and α-aminoazaheterocycle-methylglyoxal adducts and identified compounds 5a (IC50 = 71 pM), 8a,b (IC 50 = 2.5 nM), and 7a,b (IC50 = 3.4 nM) as the most potent inhibitors of WT-CFTR channels. Similar ranges of inhibition were also found when these compounds were evaluated on CFTR channels with the cystic fibrosis mutations F508del (in temperature-corrected human airway epithelial F508del/F508del CF15 cells)-, G551D-, and G1349D-CFTR (expressed in CHO and COS-7 cells). No effect of compound 5a was detected on the volume-regulated or calcium-regulated iodide efflux. Picomolar inhibition of WT-CFTR with adduct 5a was also found using a 6-methoxy-N-(3-sulfopropyl)-quinolinium fluorescent probe applied to the human tracheobronchial epithelial cell line 16HBE14o-. Finally, we found comparable inhibition by 5a or by CFTRinh-172 of forskolin-dependent short-circuit currents in mouse colon. To the best of our knowledge, these new nontoxic α-aminoazaheterocycle-methylglyoxal adducts represent the most potent compounds reported to inhibit CFTR chloride channels. Copyright
N -Glycosylation with sulfoxide donors for the synthesis of peptidonucleosides
Beau, Jean-Marie,Beretta, Margaux,Dr?ge, Thomas,Es-Sayed, Mazen,Nicolas, Lionel,Norsikian, Stéphanie,Rouchaud, Emilie,Vors, Jean-Pierre
supporting information, p. 4285 - 4291 (2021/05/31)
The synthesis of glycopyranosyl nucleosides modified in the sugar moiety has been less frequently explored, notably because of the lack of a reliable method to glycosylate pyrimidine bases. Herein we report a solution in the context of the synthesis of peptidonucleosides. They were obtained after glycosylation of different pyrimidine nucleobases with glucopyranosyl donors carrying an azide group at the C4 position. A methodological study involving different anomeric leaving groups (acetate, phenylsulfoxide and ortho-hexynylbenzoate) showed that a sulfoxide donor in combination with trimethylsilyl triflate as the promoter led to the best yields.
Preparation method for synthesizing palbociclib intermediate and method for synthesizing palbociclib
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Paragraph 0018, (2020/09/30)
The invention discloses a preparation method of a novel palbociclib intermediate. The method is characterized by comprising the following steps: taking cytosine as a raw material, through protection of the amino group of cytosine, using an acetylation agent to perform acylation to obtain a 5- acetylation product in the presence of a Lewis acid or other acidic reagents, performing de-protection toobtain 5-acetylcytosine, and performing bromo-cyclopentane substitution and methyl acetoacetate cyclization to obtain a key pyridopyrimidine intermediate, which can be used for preparing palbociclib.The method has the advantages of short reaction route, cheap and easily available cytosine serving as an initial raw material, mild reaction conditions, high total yield, suitability for industrial production, and the like.
Stereoselective N-glycosylation with N4-acyl cytosines and efficient synthesis of gemcitabine
Liu, Tongchao,Tang, Jiadeng,Liang, Jianpeng,Chen, Yabin,Wang, Xiaowen,Shen, Jingkang,Zhao, Dongmei,Xiong, Bing,Cen, Jun-Da,Chen, Yue-Lei
, p. 1203 - 1213 (2019/01/29)
Through systematical comparison of various N4-protected cytosine derivatives in the glycosylation step of gemcitabine synthesis, highly beta-stereoselective and high yielding TBAI catalyzed N-glycosylation was achieved with N4-Bz cytosine and anomeric mixture of 2,2‘-difluororibose mesylate donor. The subsequent global deprotection gave gemcitabine efficiently. Meanwhile, the anomeric chloride intermediate and fluoride-displaced side products of this N-glycosylation were identified, too. This new glycosylation method reveals the importance of N4-protection in the stereoselective preparation of pyrimidine nucleoside, also provides a potential alternative to current industrial process to gemcitabine.
Synthesis and in vitro activity of N-sulfonylamidine-derived Pyrimidine Analogues
Krstulovi?, Luka,Safti?, Dijana,Ismaili, Hamit,Baji?, Miroslav,Glava?-Obrovac, Ljubica,?ini?, Biserka
, p. 625 - 636 (2018/05/07)
Two novel series of N-sulfonylamidino pyrimidine derivatives were synthesized via Cu-catalyzed three-component reaction of propargylated nucleobases with different benzenesulfonyl azides and amines. In this way 4-acetamido, 4 -methyl and 4-carboxybenzenesulfonyl amidine products 15-26 in the uracil series and 4-acetamidobenzenesulfonyl amidine derivatives 27-29 in the cytosine series were prepared in 34-69 % yields. Attempts to prepare N-sulfonylamidino cytosine derivatives in reaction with 4-methylbenzenesulfonyl azide were unsuccessful. The cytosine derivatives 32 and 33 were prepared from the N-sulfonylamidino uracil derivatives via the C4 triazole intermediates. The prepared N-sulfonylamidino pyrimidine derivatives 1-28 were tested for the antiproliferative activity on a panel of seven tumor cell lines of different histological origin (HeLa, Caco-2, NCI-H358, Raji, HuT78, K562, Jurkat) and on normal MDCK I cells. Most of the synthesized compounds showed antiproliferative activity on the tested cell lines.
PROCESS FOR PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE
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Page/Page column 8, (2011/11/30)
The present invention relates to a novel and stereoselective synthetic process for the preparation of optically active cis-nucleoside derivatives of compound of Formula (I), wherein R3 represents H, F, Cl, C1-16 alkyl.
PROCESS FOR THE PREPARATION OF CIS-NUCLEOSIDE DERIVATIVE
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Page/Page column 18, (2010/08/08)
The present invention relates to a novel and stereoselective synthetic process for the preparation of optically active cis-nucleoside derivatives of compound of Formula (I), wherein R3 represents H, F, Cl, C1-16 alkyl.
Method for the treatment or prevention of viral infection using nucleoside analogues
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, (2008/06/13)
Compounds of formula I: wherein Y, X, R1 and Ra are defined herein are in methods for treating or preventing a viral infections selected from herpes simplex virus, varicella zoster virus, respiratory syncytial virus and cytomegalovirus infections.
