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1.
Homologation of glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. In the present work, starting from two potent and selective unnatural amino acids previously developed by us, we investigated the effects on the activity/selectivity profile produced by a further increase in the distance between the amino acidic moiety and the distal carboxylate group. Interestingly, the insertion of an aromatic ring as a spacer produced a low micromolar affinity NMDA ligand that might represent a lead for the development of a new class of NMDA antagonists.  相似文献   

2.
Glycosaminoglycans were isolated from bovine and human milk fat globule membrane (MFGM) preparations and characterized. The amount of glycosaminoglycans in human MFGM protein fraction was 5 ~ 10 times higher than that in bovine MFGM protein fraction. On Dowex-1 column chromatography most of the glycosaminoglycans were eluted with 1 M and 3 M NaCl. Cellulose acetate electrophoresis, chondroitinase digestion and nitrous acid degradation indicated that the major glycosaminoglycan in both bovine and human MFGM was heparan sulfate. Bovine MFGM was shown to contain chondroitin sulfate A/C in addition to heparan sulfate. The glycosaminoglycan composition of bovine colostral MFGM was similar to that of bovine normal MFGM. The glycosaminoglycan fraction prepared from MFGM of human colostrum, however, did not contain heparan sulfate, suggesting some compositional changes in glycosaminoglycans during the lactation period.  相似文献   

3.
The [2+2] cycloaddition reaction between a double bond from a fullerene and an oestrogen or similar organic derivative has been studied in the scheme of the ab initio atom-centred density matrix propagation molecular dynamics model. The reaction was simulated considering vacuum, a little polar medium (butyric acid) and a strong polar medium (water). The results are completely different with the change of environments; some leading to an unidentified broken species without identification, whereas others produced a defined organic complex. The reaction stages have been analysed here and possible applications for medicine are achieved.  相似文献   

4.
Fipronil is a phenyl pyrazole molecule widely used across the world as both insecticide and veterinary drug. The main goal of this work was to synthesize a fluorescently labeled fipronil derivative for cellular imaging without affecting its intrinsic properties. We selected fluorescein as fluorescent probe and we investigated different strategies for stable chemical ligation between both entities, such as thiourea and direct peptide bond. While thiourea bond displayed low stability, direct peptide bond was difficult to achieve due to problems of steric hindrance. The best result was obtained by conjugation using click chemistry, which allowed to obtain fipronil stably labeled with the fluorescent probe.  相似文献   

5.
We compare herein the scope of three copper (I) catalysts on the synthesis of various 1,4-disubstitued-1,2,3-triazolo-carbanucleosides through a microwave (and thermic) assisted Huisgen 1,3-dipolar cycloaddition. The tetrakis(acetonitrile)copper hexafluorophosphate ([Cu(CH 3 CN)4]PF 6 ), the imidazoline(mesythyl)copper bromide (Imes)CuBr, and the copper/copper sulfate Cu(0)/CuSO 4 (II) mixture have been chosen for this study. Their influence in a catalytic amount will be analyzed according to the substituent of the alkyne, the solvent, or the heating method.  相似文献   

6.
Ten N(epsilon)-glycylornithineamide derivatives have been synthesized containing various N(alpha)-linked pyrimidine-1-ylacetyl groups which can undergo (2pi + 2pi) photodimerization on irradiation with UV light at 254 nm. The dimerization efficiency of the free and bound pyrimidine groups was compared in aqueous solution: it was dependent on the substitution of the pyrimidine ring. N(alpha),N(alpha')-bis-(uracil-1-ylacetyl)-(N(epsilon)-glycylornithineamide) and N(alpha),N(alpha')-bis-(5-bromouracil-1-ylacetyl)-(N(epsilon)-glycylornithineamide) were identified as possible candidates for optical data storage.  相似文献   

7.
An efficient and facile synthesis of 17-pyrazolinyl derivatives of pregnenolone and their evaluation as potential anticancer agents against various human cancer cell lines are reported. The scheme involves the transformation of the starting pregnenolone acetate into pregnenolone, conversion of pregnenolone to the corresponding benzylidine derivatives and finally the conversion of this derivative to the stable steroidal 17-pyrazoline. Various compounds 4b, 4c, 4e, 4f, 4h and 4j showed significant cytotoxic activity especially against HT-29, HCT-15, 502713 cell lines.  相似文献   

8.
A convenient and modular synthesis involving diastereoselective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction was carried out to furnish 1,4-disubstituted-1,2,3-triazoles of Ludartin. This reaction scheme involving Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction leading to the formation of triazolyl analogs is being reported for the first time. All the triazolyl products were characterised using spectral data analysis. Sulphorhodamine B cytotoxicity screening of the resulting products against a panel of five human cancerous cell-lines revealed that few of the analogs display promising broad spectrum cytotoxic effect. Among all the synthesized compounds, only 3q displayed the best cytotoxic effect with IC50 values of 12, 11, 38, 39 and 8.5 μM but less than the standard Ludartin (1) with IC50 values of 6.3, 7.4, 7.5, 6.9 and 0.5 μM against human neuroblastoma (T98G), lung (A-549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell lines, respectively. The present synthesis was designed based on the previous literature reports of Ludartin as an aromatase inhibitor. Our work provides an initial study on structure–activity relationship of triazolyl analogs of sesquiterpene lactones in general and Ludartin (1) in particular.  相似文献   

9.
Abstract

The synthesis of new 3′-deoxy-3′-[4-(pyrimidin-1-yl)methyl-1,2,3-triazol-1-yl]thymidine 6a–f, from 3′-azido-3′-deoxy-5′-O-monomethoxytrityl-thymidine is described. The key step is the 1,3-dipolar cycloaddition between the azido group of the protected AZT 3 and N-1-propargylpyrimidine derivatives 2a–f. All new derivatives 6a–f were evaluated for their inhibitory effects against the replication of HIV-1 (IIIB), HIV-2 (ROD). No marked activity was found.  相似文献   

10.
5-Aryl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesised from N-methyl-C-diethoxyphosphorylnitrone and vinyl aryls in good yields. Isoxazolidine phosphonates obtained herein were evaluated for activity against a broad range of DNA and RNA viruses. None of the compounds were endowed with antiviral activity nor cytostatic activity at 100 to 250 μM concentrations.  相似文献   

11.
Thunberg L  Allenmark S 《Chirality》2003,15(5):400-408
The bicyclic, C(2)-symmetric dicarboxylic acid obtained from the cycloaddition of fumaric acid to anthracene can readily be prepared in enantiomerically pure form on a large scale. Conversion of either enantiomer of the diacid into its corresponding bis-allylamide yields a selector unit, used as a building block in the synthesis of a chiral stationary phase (CSP). The terminal C-C double bonds in the selector unit were used in a hydrosilylation reaction involving a multifunctional hydrosilane to effect polymerization, crosslinking, and immobilization to the vinyl-silica used as support. A study of the enantiomer-discriminating abilities of the new CSP was made. Large separation factors were obtained for a series of benzodiazepinones, which were studied in further detail by the use of different retention modifiers. To some extent, rationalization of retention data has been achieved in terms of competition for hydrogen bonding.  相似文献   

12.
The 1,3-dipolar cycloaddition of cyclic nitrone derived from tartaric acid and (S)-5-hydroxymethyl-2(5H)-furanone leads to a single adduct which was transformed into 2,6-dihydroxyhastanecine via reaction sequence involving reduction of the lactone moiety, glycolic cleavage of the terminal diol, and the N-O hydrogenolysis followed by the intramolecular alkylation of the nitrogen atom.  相似文献   

13.
2,3,4,6-Tetra-O-acetyl-beta-D-glucopyranosyl azide is available on large scale from D-glucose by means of a three-step sequence involving acetylation, activation as the glycosyl bromide, and stereospecific displacement with azide anion. The azide functionality then serves as a convenient anchor upon which to introduce new functionality, usually with retention of the beta-stereochemistry. Here we report the synthesis of an amide-linked N-glycosyl trimer, by employing a Staudinger-aza-Wittig process on the azide, as well as a hybrid N-glycosyl triazole-amide-linked trimer in which the sugars are separated by 1,2,3-triazole heterocycles. Both of these neoglycotrimers are isolated in good yield with high beta-selectivity in each case.  相似文献   

14.
A series of novel trisubstituted 1,2,3-triazole purine nucleosides were efficiently synthesized via Huisgen 1,3-dipolar cycloaddition in good yields. Bioactivity against cytomegalovirus (CMV) and varicella-zoster virus (VZV) in human embryonic lung cell cultures was evaluated and all compounds show low antiviral activity.  相似文献   

15.
Abstract

1-(2,3-Dideoxy-2-C-hydroxymethyl-β-D-threo-pentofuranosyl)-, 1-(2,3-didehydro-2,3-dideoxy-2-C-hydroxymethyl-β-D-glycero-pentofuranosyl)- and 1-(2-C-azidomethyl-2,3-didehydro-2,3-dideoxy-β-D-glycero-pentofuranosyl)uracuracil, thymine and cytosine were synthesized and evaluated for their anti-HIV activities. A key step of the synthesis involves a novel alcohol transposition of2-methylene-nucleoside analogues.  相似文献   

16.
17.
Aryl or sugar azides were treated with allenylmagnesium bromide to generate 1,5-disubstituted-butynyl-N-aryl or N-glycosyl-1,2,3-bistriazoles in a domino fashion. Upon Cu(I) catalyzed 1,3-dipolar cycloaddition with sugar azides, these compounds afford novel unsymmetrical bis-1,2,3-triazoles in high yields.  相似文献   

18.
Breast cancer is the most incident and mortal cancer type in women, with an estimated 2 million new cases expected by 2020 worldwide, with 600,000 deaths. As not all breast cancer types respond to the anti-hormonal therapy, the development of new antineoplastic drugs is necessary. Lawsone (2-hydroxy-1,4-naphtoquinone) is a natural bioactive naphtoquinone displaying a range of activities, with dozens of derivatives described in the literature, including some glycosides possessing antitumor activity. Here, a series of glycosides of lawsone are reported for the first time and all compounds displayed good activity against the SKBR-3 cell line, with IC50 below 10 µM. The most promising derivative was the glycosyl triazole derived from peracetylated d-glucose (11), which showed better cytotoxicity against SKBR-3 (IC50 = 0.78 µM), being the most selective toward this tumoral cell (SI > 20). All compounds described in this work were more active than lawsone, indicating the importance of the carbohydrate and glycosyl triazole moiety for activity.  相似文献   

19.
A series of 5-substituted 3-phosphonylated isoxazolidines have been obtained via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-heteroaromatic acrylamides. Good trans/cis diastereoselectivities (d.e. 58–76%) of isomeric (3-diethoxyphosphoryl)isoxazolidines were observed. cis- and trans-Isoxazolidine phosphonates were evaluated for their antiviral activity against a broad range of DNA and RNA viruses but were found inactive. Their cytostatic activity toward L1210, CEM, and HeLa cells was also established, and compounds cis-12r and trans-11r having a 2,2-difluorobenzo[d][1,3]dioxole moiety slightly inhibited proliferation of HeLa cells at IC50 values of 186 and 179 μM, respectively.  相似文献   

20.
Synthesis of a novel class of natural product inspired cinnamyl-containing 1,4,5-triazole and the potent inhibition of human aromatase (CYP 450 19A1) by select members is described. Structure–activity data generated provides insights into the requirements for potency particularly the inclusion of an aryl bromide or chloride residue as a keto-bioisostere.  相似文献   

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