Transition metal complexes with Girard reagent-based ligands. Part IV. Synthesis and characterization of pyridoxilidene Girard-T hydrazone complexes. Crystal structure of the copper(II) complex

The monoligand complexes of the formula M(HPLGT)(NCS)(2) (M = Cu(II), Zn(II)) in which the ligand tridentate ONO pyridoxilidene Girard-T hydrazone, [H(3)PLGT]Cl(2) center dot 2H(2)O, was coordinated in neutral doubly deprotonated form were synthesized. Also, the first complexes with the ligand coordinated in triply deprotonated monoanionic form of the formula [Cu(PLGT)N(3)] and [Co(PLGT)(NO(2))(2)NH(3)] center dot 3H(2)O are reported. The single crystal X-ray analysis of [Cu(HPLGT)(NCS)(2)] showed that Cu(II) is placed in a square-pyramidal surrounding consisting of one tridentate Schiff base and one NCS group in the basal plane and the other NCS group in the apical position. Intermolecular hydrogen bonds leading to centrosymmetrical dimerization of these complexes were discussed. In the reaction of Girard-T and Hacac in the presence of CuCl(2), a mixture of single crystal complexes of the composition [Cu(3,5-Me(2)pz)(2)Cl(2)](2) and [Cu(acac)(2)] center dot 2[Cu(3,5-Me(2)pz)(2)Cl(2)] was obtained and X-ray analysis of the latter one was reported

Transition metal complexes with thiosemicarbazide-based ligands. Part 49. New complexes of iron(III) with deprotonated tridentate Schiff base pyridoxal derivatives

Three new bis(ligand) iron(III) complexes were prepared with the deprotonated ONX ligands (X = O,S,N), pyridoxal semi-, thiosemi- and S-methylisothiosemicarbazones (H2L1, H2L2 andH2L3, respectively) of the formulas [Fe(HL1,2)L1,2]. 4H2O and [Fe(HL3)2]OAc. 2H2O. The compounds were characterized by elemental analysis, conductometric and magnetochemical measurements, as well as by IR and UV-vis spectra. Detailed voltammetric investigations were carried out in DMF solutions in the presence of several supporting electrolytes to study the nature of the electrochemical processes and solution equilibria

Transition metal complexes with thiosemicarbazide-based ligands. Part 47. Synthesis, physicochemical and voltammetric characterization of iron(III) complexes with pyridoxal semi-, thiosemi- and S-methylisothiosemicarbazones

The reaction of warm EtOH solutions of FeX3·nH2O (X = Cl, NO3) with tridentate ONX (X = O, S, N) pyridoxal semi-, thiosemi- and S-methylisothiosemicabazones (H2L1, H2L2, H2L3, respectively) yielded high-spin octahedral mono- and bis(ligand) complexes of the formula [Fe(H2L1-3)Cl2(H2O)]Cl, [Fe(HL1,2)2]Cl·nH2O and [Fe(H2L3)(HL3)](NO3)2·H2O. The compounds were characterized by elemental analysis, conductometric and magnetochemical measurements, IR and UV-Vis spectra. Besides, a detailed voltammetric study of the complexes was carried out in DMF solution in the presence of several supporting electrolytes, to characterize the nature of the electrode processes and solution equilibria

Transition metal complexes with Girard reagent-based ligands. Part III. Synthesis and characterization of salicylaldehyde Girard-T hydrazone complexes. Crystal structure of ligand and two isostructural copper(II) complexes

The ligand, salicylaldehyde Girard-T hydrazonium chloride, [H(2)SalGT]Cl (1), and two complexes [Cu(HSalGT)X-2]center dot H2O (X = Br(2); Cl(3)) were synthesized and their crystal structures were determined by single-crystal X-ray analysis. In the two isostructural complexes, the Cu(II) is located in a square-pyramidal environment, with the chelating ligand and one halogen atom in the basal plane and the second halogen in the apical position. The most apparent structural difference between the 1 and its complexes 2 and 3 is the orientation of the N(CH3)(3) group: in 1, it is practically coplanar to the rest of the molecule, while in 2 and 3 it is oriented to the side of the axially bonded halogen, which can be explained by the C-H center dot center dot center dot X intramolecular interactions. The compounds were characterized by elemental analysis, molar conductivity, magnetic susceptibility and electronic absorption spectra

The synthesis, pharmacological evaluation and conformational analysis of (+/-)cis- and (+/-)trans3-carbomethoxy fentanyl-"iso-carfentanil"

A novel analogue of fentanyl, 3-carbomethoxyfentanyl, or "iso-carfentanil", was synthesized by a simple and efficient route. In the first step phenethylamine was condensed with two equivalents of methyl acrylate to afford the amino-diester Ib in quantitative yield. Dieckmann cyclization of this intermediate yielded 3-carbomethoxy N-phenethyl-4-piperidone 2 in ca. 80% yield, after mild hydrolysis. Condensation of this beta-keto ester with aniline in acetic acid gave the stable enamine 3 (70% yield) which was then reduced with NaBH3CN in methanol at pH approximate to 5, to yield 4-anilino-3-carbomethoxy-N-phenethyl piperidine, quantitatively. This intermediate was obtained as a 50:50 mixture of the (+/-) cis and (+/-) trans isomers, 4a and 4b, respectively. After the mixture of diastereoisomers was separated on a neutral aluminium oxide column, the pure 4a and 4b isomers were acylated with propionyl chloride, thus completing the synthesis of 3-carbomethoxy fentanyl 5a and 5b. The relative stereochemistry was H-1-NMR spectroscopy. These compounds present regioisomers of determined by carfentanil, one of the most potent narcotic analgesic known to date. Preliminary pharmacological evaluation (tail-withdrawal test in rats) revealed substantially reduced potency of both diastereoisomers, the (+/-) trans 5b in particular, compared to carfentanil. The computational (molecular mechanics) search of the low energy regions of the conformational space of the cis 5a and trans 5b isomers revealed the difference in their conformational mobility. Besides being more conformationaly flexible, the trans isomer has unfavorable orientation of the 4-N-phenylpropanamide group compared to the other active analogs of fentanyl. This is believed to be the reason of its reduced potency relative to fentanyl

The synthesis, pharmacological evaluation and conformational analysis of (+/-)cis- and (+/-)trans3-carbomethoxy fentanyl-"iso-carfentanil"

A novel analogue of fentanyl, 3-carbomethoxyfentanyl, or "iso-carfentanil", was synthesized by a simple and efficient route. In the first step phenethylamine was condensed with two equivalents of methyl acrylate to afford the amino-diester Ib in quantitative yield. Dieckmann cyclization of this intermediate yielded 3-carbomethoxy N-phenethyl-4-piperidone 2 in ca. 80% yield, after mild hydrolysis. Condensation of this beta-keto ester with aniline in acetic acid gave the stable enamine 3 (70% yield) which was then reduced with NaBH3CN in methanol at pH approximate to 5, to yield 4-anilino-3-carbomethoxy-N-phenethyl piperidine, quantitatively. This intermediate was obtained as a 50:50 mixture of the (+/-) cis and (+/-) trans isomers, 4a and 4b, respectively. After the mixture of diastereoisomers was separated on a neutral aluminium oxide column, the pure 4a and 4b isomers were acylated with propionyl chloride, thus completing the synthesis of 3-carbomethoxy fentanyl 5a and 5b. The relative stereochemistry was H-1-NMR spectroscopy. These compounds present regioisomers of determined by carfentanil, one of the most potent narcotic analgesic known to date. Preliminary pharmacological evaluation (tail-withdrawal test in rats) revealed substantially reduced potency of both diastereoisomers, the (+/-) trans 5b in particular, compared to carfentanil. The computational (molecular mechanics) search of the low energy regions of the conformational space of the cis 5a and trans 5b isomers revealed the difference in their conformational mobility. Besides being more conformationaly flexible, the trans isomer has unfavorable orientation of the 4-N-phenylpropanamide group compared to the other active analogs of fentanyl. This is believed to be the reason of its reduced potency relative to fentanyl

The genesis of the Faculty of Community Medicine (now the Faculty of Public Health Medicine) of the Royal Colleges of Physicians of the United Kingdom

SIGLEAvailable from British Library Document Supply Centre-DSC:q97/03431 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma.

The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and p<0.001, respectively). Furthermore, 22% of all recruited cRCC patients were carriers of combined GSTM1-null, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04). Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as "risk-carrying genotype combination" in cRCC