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101.
J Moron M Rautureau C Huel A Pierré LK Berthier G Atassi E Bisagni 《Canadian Metallurgical Quarterly》1993,8(6):399-416
2-Acetyl-4-chloro-3-lithiopyridine ethylene glycol ketal (6b) was reacted with 3-formyl-5-methoxy-1-methyl-indole (9) and 3-formyl-1-methyl-1H-pyrrolo [3,2-c] pyridine (12), giving the corresponding expected alcohols. Reduction of these intermediates with triethylsilane trifluoroacetic acid and subsequent cyclodehydration then led to 4-chloro-7-methoxy-10,11-dimethyl-10H-pyrido [2,3-b] carbazole (8a) and the corresponding 7-aza-analog (8b). The synthesis of 4-chloro-11-methyl (and 5,11-dimethyl)-10-unsubstituted derivatives of these two series was performed through an independent pathway, involving condensation of conveniently substituted 2-amino carbazoles (17) and 7-amino-5H-pyrido [4,3-b] indoles (18) with 5-(ethoxymethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione, thermal cyclization of the resulting compounds with concomitant decarboxylation to the corresponding tetracyclic fused-4-quinolone systems and final chlorination with phosphorus oxychloride. Nucleophilic substitution of various 4-chloro derivatives was then easily performed in an excess of the required dialkylamino alkylamines at reflux and 4-amino substituted-7-hydroxy-10H- pyrido [2,3-b] carbazoles (25d-e) were obtained from 7-methoxy precursors (25a-b), by demethylation with boron tribromide in methylene chloride at -65 degrees C or with boiling 47% hydrobromic acid. Cytotoxicity determination of all new aminosubstituted derivatives and in vivo antitumor evaluation of the most active compounds clearly show that these two series of ellipticine analogs closely related to highly active products are devoid of antitumor properties in two experimental models shown to be sensitive to ellipticines. The place of the pyridinic nitrogen atom in these series has thus been demonstrated to play a crucial role in antitumor activity. 相似文献
102.
103.
M.F. Stamp 《Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms》1985,9(4):513-515
The 1s2s3S?1s2p3PJ (J = 0, 1, 2) transitions in helium-like ions can be used to test QED, but only if the other contributions to the transition energy, and especially the relativistic contributions are known to high accuracy.This work tests the relativistic calculations by comparing the theoretical splittings (which are nearly ndependent of QED) with each other and with experiment. An estimate of the largest uncalculated relativistic term, of relative order α4Z4, is also made.It is found that the calculations of Hata and Grant are not very accurate, and that the small discrepancy between Drake and experiment vanishes if the α4Z4 relativistic term is included. 相似文献
104.
AJ Black HL McLeod HA Capell RH Powrie LK Matowe SC Pritchard ES Collie-Duguid DM Reid 《Canadian Metallurgical Quarterly》1998,129(9):716-718
BACKGROUND: Substantial hematologic toxicity limits the use of azathioprine. OBJECTIVE: To evaluate 1) polymorphic inactivation of azathioprine by thiopurine methyltransferase and 2) clinical toxicity. DESIGN: Prospective cohort study. SETTING: Two rheumatology units. PATIENTS: 67 patients for whom azathioprine was prescribed as second-line therapy for rheumatic disease. MEASUREMENTS: Polymerase chain reaction-based assays were used to detect mutations in thiopurine methyltransferase. The primary end point was discontinuation of azathioprine therapy because of toxicity. RESULTS: Six of 67 patients (9%) were heterozygous for mutant thiopurine methyltransferase alleles. Five of the 6 patients discontinued therapy within 1 month of starting treatment because of low leukocyte counts. The sixth patient did not adhere to treatment. Patients with wild-type thiopurine methyltransferase alleles received therapy longer than did patients with mutant alleles (median duration of therapy, 39 weeks [range, 6 to 180 weeks] and 2 weeks [range, 2 to 4 weeks], respectively; P = 0.018). CONCLUSION: Analysis of thiopurine methyltransferase genotype is a quick way to identify patients at risk for acute toxicity from azathioprine. 相似文献
105.
106.
Two new porphinoids, tolyporphins J (1) and K (2), have been isolated from the terrestrial cyanobacterium, Tolypothrix nodosa (HT-58-2) and identified by NMR and mass spectral analysis. The activities of tolyporphins J and K in cell sensitization and drug accumulation assays for multidrug resistance (MDR) reversal were compared with those of tolyporphin A. Unusual NMR spectroscopic shifts were observed for tolyporphin J (1) in CDCl3. 相似文献
107.
108.
KJ Yarema LK Mahal RE Bruehl EC Rodriguez CR Bertozzi 《Canadian Metallurgical Quarterly》1998,273(47):31168-31179
The development of chemical strategies for decorating cells with defined carbohydrate epitopes would greatly facilitate studies of carbohydrate-mediated cell surface interactions. This report describes a general strategy for engineering the display of chemically defined oligosaccharides on cell surfaces that combines the concepts of metabolic engineering and selective chemical reactivity. Using a recently described method (Mahal, L. K., Yarema, K. J., and Bertozzi, C. R. (1997) Science 276, 1125-1128), we delivered a uniquely reactive ketone group to endogenous cell surface sialic acid residues by treating cells with the ketone-bearing metabolic precursor N-levulinoylmannosamine (ManLev). The ketone undergoes highly selective condensation reactions with complementary nucleophiles such as aminooxy and hydrazide groups. The detailed quantitative parameters of ManLev metabolism in human and nonhuman-derived cell lines were determined to establish a foundation for the modification of cell surfaces with novel epitopes at defined cell-surface densities. Ketones within the glycoconjugates on ManLev-treated cells were then reacted with synthetic aminooxy and hydrazide-functionalized carbohydrates. The remodeled cells were endowed with novel lectin binding profiles as determined by flow cytometry analysis. The simplicity and generality of this method make it well suited for use in the study of carbohydrate-mediated cell surface interactions. 相似文献
109.
110.