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1.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):617-621
Abstract In this paper a short account of our recent research concerning the development of new synthetic methods and reagents for the preparation of nucleotides and their analogues, is given. 相似文献
2.
Karel Pomeisl Květoslava Horská Radek Pohl Jiří Blažek Marcela Krečmerová 《Nucleosides, nucleotides & nucleic acids》2013,32(3):159-171
A series of new monophosphates of 1-[2-(phosphonomethoxy)alkyl]thymines, such as PMPTp, 3-MeO-PMPTp, HPMPTp, and FPMPTp, were synthesized and tested for their ability to inhibit human thymidine phosphorylase. Kinetic measurements of enzyme activity were performed using thymidine and inorganic phosphate as the substrates. The data show that some monophosphates provide a considerable increase of the multisubstrate inhibitory effect. The highest inhibitory potency was found with (R)-FPMPTp 4c (K i dT = 4.09 ± 0.47 μM, K i(Pi) = 2.13 ± 0.29 μM) and (R) 3-MeO-PMPTp 4d (K i dT = 5.78 ± 0.71 μM, K i(Pi) = 2.71 ± 0.37 μM). 相似文献
3.
The preparation of an unprecedented series of nucleobase modified 3‐fluoro‐2‐(phosphonomethoxy)propyl (FPMP) acyclic nucleosides in both their (R) and (S) enantiomerically pure forms is described. The synthesis focuses on a Mitsunobu alkylation reaction to construct the C?N(9) bond between a chiral fluorinated side‐chain residue and 6‐ or 7‐modified guanine analogs. Prodrugs of FPMP‐7‐deazaguanine were also synthesized by derivatization of the corresponding phosphonic acid functionality with (bis)diamyl aspartate amidate groups, leading to moderate activity against human immunodeficiency virus type 1 (HIV‐1). 相似文献
4.
New aziridine 2‐phosphonic acids were prepared by monohydrolysis of the aziridine 2‐phosphonates that were obtained by the modified Gabriel?Cromwell reaction of vinyl phosphonate or α‐tosylvinyl phosphonate with a primary amine or a chiral amine. The cellular cytotoxicity of these compounds was tested against the HCT‐116 colorectal cancer cell lines and the CCD‐18Co normal colon fibroblast lines using the MTT assay. Three of the synthesized phosphonic acid derivatives 2e (ethyl hydrogen {(2S)‐1‐[(1S)‐1‐(naphthalen‐2‐yl)ethyl]aziridin‐2‐yl}phosphonate), 2h (ethyl hydrogen (1‐benzylaziridin‐2‐yl)phosphonate), and 2i (ethyl hydrogen (1‐cyclohexylaziridin‐2‐yl)phosphonate) showed higher cytotoxicity than the reference cancer treatment agent etoposide. Cell death was through a robust induction of apoptosis even more effectively than etoposide, a well‐known apoptosis inducing agent. 相似文献
5.
Aleksandrova L. A. Andronova V. L. Karpenko I. L. Skoblov Yu. S. Adani A. Galegov G. A. 《Russian Journal of Bioorganic Chemistry》2002,28(5):412-418
A number of new 5"-phosphonate derivatives of 4"-thio-5-ethyl-2"-deoxyuridine (TEDU) were synthesized. These compounds displayed a low cytotoxicity and, except for TEDU 5"-fluorophosphate, antiherpes activity similar to that of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (pencyclovir). 5"-Ethoxycarbonylphosphonate and 5"-aminocarbonylphosphonate of TEDU were also found to suppress the reproduction of herpes simplex type 1 virus, which is resistant to acyclovir. 相似文献
6.
Organocatalytic enantioselective synthesis of α‐indolyl phosphonates has been successfully carried out via asymmetric Friedel‐Crafts alkylation of substituted indoles with (E)‐dialkyl 3‐oxoprop‐1‐enylphosphonates in 48–82% yield and 73–96% ee. Chirality, 2009. © 2008 Wiley‐Liss, Inc. 相似文献
7.
Dana Hockov Antonín Holý Milena Masojídkov Dianne T. Keough John de Jersey Luke W. Guddat 《Bioorganic & medicinal chemistry》2009,17(17):6218-6232
The malarial parasite Plasmodium falciparum (Pf) lacks the de novo pathway and relies on the salvage enzyme, hypoxanthine–guanine–xanthine phosphoribosyltransferase (HGXPRT), for the synthesis of the 6-oxopurine nucleoside monophosphates. Specific acyclic nucleoside phosphonates (ANPs) inhibit PfHGXPRT and possess anti-plasmodial activity. Two series of novel branched ANPs derived from 9-[2-(2-phosphonoethoxy)ethyl]purines were synthesized to investigate their inhibition of PfHGXPRT and human HGPRT. The best inhibitor of PfHGXPRT has a Ki of 1 μM. The data showed that both the position and nature of the hydrophobic substituent change the potency and selectivity of the ANPs. 相似文献
8.
M. V. Jasko A. V. Shipitsyn A. L. Khandazhinskaya E. A. Shirokova P. N. Sol’yev O. A. Plyasunova A. G. Pokrovskii 《Russian Journal of Bioorganic Chemistry》2006,32(6):542-546
New 5′-phosphonates of 3′-azido-3′-deoxythymidine were synthesized and shown to be low-toxic and markedly active in MT-4 cell cultures infected with HIV-1. 相似文献
9.
Enantioseparation of α‐Hydroxyallylphosphonates and Phosphonoallylic Carbonate Derivatives on Chiral Stationary Phases Using Sequential UV,Polarimetric, and Refractive Index Detection
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Bruce C. Hamper Michael P. Mannino Melissa E. Mueller Liam T. Harrison Christopher D. Spilling 《Chirality》2016,28(9):656-662
Chromatographic separation of the enantiomers of parent compounds dimethyl α‐hydroxyallyl phosphonate 1a and 1‐(dimethoxyphosphoryl) allyl methyl carbonate 1b was demonstrated by high‐performance liquid chromatography (HPLC) using Chiralpak AS‐H and ad ‐H chiral stationary phases (CSP), respectively, using a combination of UV, polarimetric, and refractive index detectors. A comparison was made of the separation efficiency and elution order of enantiomeric α‐hydroxyallyl phosphonates and their carbonate derivatives on commercially available polysaccharide AS, ad , OD, IC‐3, and Whelk‐O 1 CSPs. In general, the α‐hydroxyallyl phosphonates were resolved on the AS‐H CSP, whereas the carbonate derivatives 1b and 2b were preferentially resolved on the ad ‐H CSP. The impact of aryl substitution on the resolution of analytes 1d , 1e , 1f and 2 , 3 , 4 , 5 , 6 , 7 , 8 was evaluated. Thermodynamic parameters determined for enantioselective adsorption hydroxyphosphonates 1a and 4 on the AS‐H CSP and carbonate 1b on the ad ‐H CSP demonstrated enthalpic control for separation of the enantiomers. Chirality 28:656–662, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
10.
Alternate modes of binding in two crystal structures of alkaline phosphatase-inhibitor complexes
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Holtz KM Stec B Myers JK Antonelli SM Widlanski TS Kantrowitz ER 《Protein science : a publication of the Protein Society》2000,9(5):907-915
Two high resolution crystal structures of Escherichia coli alkaline phosphatase (AP) in the presence of phosphonate inhibitors are reported. The phosphonate compounds, phosphonoacetic acid (PAA) and mercaptomethylphosphonic acid (MMP), bind competitively to AP with dissociation constants of 5.5 and 0.6 mM, respectively. The structures of the complexes of AP with PAA and MMP were refined at high resolution to crystallographic R-values of 19.0 and 17.5%, respectively. Refinement of the AP-inhibitor complexes was carried out using X-PLOR. The final round of refinement was done using SHELXL-97. Crystallographic analyses of the inhibitor complexes reveal different binding modes for the two phosphonate compounds. The significant difference in binding constants can be attributed to these alternative binding modes observed in the high resolution X-ray structures. The phosphinyl group of PAA coordinates to the active site zinc ions in a manner similar to the competitive inhibitor and product inorganic phosphate. In contrast, MMP binds with its phosphonate moiety directed toward solvent. Both enzyme-inhibitor complexes exhibit close contacts, one of which has the chemical and geometrical potential to be considered an unconventional hydrogen bond of the type C-H...X. 相似文献