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1.
Shevchenko VP Nagaev IIu Kuznetsov IuV Polunin EV Zozulia AA Miasoedov NF 《Bioorganicheskaia khimiia》2005,31(4):420-424
A synthesis of olanzapine, 2-methyl-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine was carried out, and the conditions for its tritium labeling were optimized, to get a tritium-labeled olanzapine preparation with molar radioactivity of 12 Ci/mmol. 相似文献
2.
New analogues of 3β-hydroxy-5α-cholest-8(14)-en-15-one (15-ketosterol) with modified 17-chains [(22S,23S,24S)- and (22R,23R,24S)-3β-hydroxy-24-methyl-22,23-oxido-5α -cholest-8(14)-en-15- ones and (22RS,23ξ,24S)-24-methyl-5α-cholesta-8(14)-ene-3β, 22,23-triol-15-one] were synthesized from (22E,24S)-3β-acetoxy-24-methyl-5α-cholesta-8(14), 22-dien-15-one. The chiralities of their 22 and 23 centers were determined by NMR spectroscopy. The isomeric 22,23-epoxides effectively inhibited cholesterol biosynthesis in hepatoma Hep G2 cells (IC50 0.9±0.2 and 0.7±0.2 μM, respectively), and their activities significantly exceeded those of 15-ketosterol (IC50 4.0±0.5 μM), (22E,24S)-3β-hydroxy-24-methyl-5α-cholesta-8(14),22- dien-15-one (IC50 3.1±0.4 μM), and the 3β,22,23-triol synthesized (IC50 6.0±1.0 μM).__________Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 3, 2005, pp. 312–319.Original Russian Text Copyright © 2005 by Flegentov, Piir, Medvedeva, Tkachev, Timofeev, Misharin. 相似文献
3.
T. V. Malyarenko A. A. Kicha N. V. Ivanchina A. I. Kalinovsky P. S. Dmitrenok A. V. Smirnov 《Russian Journal of Bioorganic Chemistry》2010,36(6):755-761
Thirteen steroidal compounds including three new polyhydroxysteroids, (24R,25S)-24-methyl-5α-cholestane-3β,6α,8,15β,16β,26-hexaol, (22E,24R,25S)-24-methyl-5α-cholest-22-ene-3β,6α,8,15β,16β,26-hexaol, and (22E,24R,25S)-24-methyl-5α-cholest-22-ene-3β,4β,6α,8,15β,16β,26-heptaol, have been isolated along with ten previously known polyhydroxysteroids
from the tropical starfish Asteropsis carinifera collected near the coast of Vietnam. The structures of the new compounds were elucidated by spectroscopic methods (mainly
2D NMR and ESI mass spectrometry). 相似文献
4.
David W. Boulton John S. Markowitz C. Lindsay DeVane 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,759(2):319-323
Olanzapine is a commonly used atypical antipsychotic medication for which therapeutic drug monitoring has been proposed as clinically useful. A sensitive method was developed for the determination of olanzapine concentrations in plasma and urine by high-performance liquid chromatography with low-wavelength ultraviolet absorption detection (214 nm). A single-step liquid–liquid extraction procedure using heptane-iso-amyl alcohol (97.5:2.5 v/v) was employed to recover olanzapine and the internal standard (a 2-ethylated olanzapine derivative) from the biological matrices which were adjusted to pH 10 with 1 M carbonate buffer. Detector response was linear from 1–5000 ng (r2>0.98). The limit of detection of the assay (signal:noise=3:1) and the lower limit of quantitation were 0.75 ng and 1 ng/ml of olanzapine, respectively. Interday variation for olanzapine 50 ng/ml in plasma and urine was 5.2% and 7.1% (n=5), respectively, and 9.5 and 12.3% at 1 ng/ml (n=5). Intraday variation for olanzapine 50 ng/ml in plasma and urine was 8.1% and 9.6% (n=15), respectively, and 14.2 and 17.1% at 1 ng/ml (n=15). The recoveries of olanzapine (50 ng/ml) and the internal standard were 83±6 and 92±6% in plasma, respectively, and 79±7 and 89±7% in urine, respectively. Accuracy was 96% and 93% at 50 and 1 ng/ml, respectively. The applicability of the assay was demonstrated by determining plasma concentrations of olanzapine in a healthy male volunteer for 48 h following a single oral dose of 5 mg olanzapine. This method is suitable for studying olanzapine disposition in single or multiple-dose pharmacokinetic studies. 相似文献
5.
Metabolic pathways of quinoline, indole and their methylated analogs by Desulfobacterium indolicum (DSM 3383) 总被引:2,自引:0,他引:2
S. S. Johansen D. Licht E. Arvin H. Mosbæk A. B. Hansen 《Applied microbiology and biotechnology》1997,47(3):292-300
The transformation of quinoline, isoquinoline and 3-, 4-, 6- and 8-methylquinoline by Desulfobacterium indolicum was compared with that of the N-containing analogues indole and 1-, 2-, 3- and 7-methylindole. The metabolites were identified
using high-performance liquid chromatography with UV detection, thin-layer chromatography, combined gas chromatography/mass
spectrometry and proton NMR spectroscopy. All degraded compounds were initially hydroxylated at position 2 by D. indolicum. A new degradation product of quinoline was observed in the second transformation step, where 3,4-dihydro-2-quinolinone accumulated.
This ring-reduced compound was further transformed into unidentified products. The transformation pathway of indole was characterized
by well-known steps through oxindole, isatin, and anthranilic acid. No further transformation of the hydroxylated methyl analogues:
3- and 7-methyloxindole and 3- and 4-methyl-2-quinolinone, was observed within 162 days of incubation. These degradation products
accumulated in stoichiometric amounts, while 6- and 8-methyl-2-quinolinone were further degraded to 6- and 8-methyl-3,4-dihydro-2-quinolinone
in stoichiometric amounts. Isoquinoline, 2-methylquinoline and 1- and 2-methylindole were not degraded by D. indolicum. These observations indicate that a methyl group at or close to position 2 results in blockage of the microbial attack, and
that transformation of hydroxyquinolines methylated at the heterocyclic ring also was blocked or sterically inhibited. An
incomplete transformation of some methylated compounds was observed, e.g. for 3- and 6-methylquinoline and 3- and 7-methylindole,
with residual concentrations of 0.5–4 mg/l in relation to initial concentrations of 10–15 mg/l.
Received: 23 July 1996 / Received revision: 4 October 1996 / Accepted: 25 October 1996 相似文献
6.
Synthesis and antimicrobial activity of novel 1-methyl-3-alkylthio-4-aminoquinolinium salts 2 and 1-methyl-3-acylthio-4-aminoquinolinium salts 4 are described. Compounds 2 were obtained by reacting 1-methyl-3,4-(dimethylthio)quinolinium chloride 1 with amines and by reacting 1-methyl-4-aminoquinolinium-3-thiolates 3 with alkylating agents. Compounds 4 were obtained by the reaction of 1-methyl-4-aminoquinolinium-3-thiolates 3 with acylating agents. Antimicrobial activity of compounds 2 and 4 was determined using G+ (Staphylococcus aureus, Enterococcus faecalis) and G− (Escherichia coli, Pseudomonas aeruginosa) strains as well as Candida albicans yeast. The compounds show greatest activity against S. aureus whereas the lowest against P. aeruginosa. 相似文献
7.
Masaharu Konishi Yoshio Mori Kentaro Hirai 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1982,229(2)
A gas—liquid chromatographic method for the simultaneous determination of triazolobenzophenone [2′,5-dichloro-2-(3-glycylaminomethyl-5-methyl-4H-1,2,4-triazol-4-yl)-benzophenone, TB] and its major blood metabolite, triazolam, 8-chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine (TZ), in monkey plasma was developed. Decomposition of TB was observed during gas—liquid chromatography. In alkaline medium, TB in plasma was submitted to ring closure reaction to yield triazolo-aminoquinoline, [4-amino-7-chloro-5-(2-chlorophenyl)-1-methyl-4H-s-triazolo[4,3-a]quinoline (TAQ), while TZ remained unaffected, and TAQ and TZ in the benzene extract were assayed by gas—liquid chromatography using an electron-capture detector. The concentration ranges studied were from 5 to 40 ng of TB per 0.5 ml of plasma and from 2 to 20 ng of TZ per 0.5 ml of plasma. This method could be applied to the determination of the plasma levels of TB and TZ in monkeys following intravenous administration of a single 0.2 mg/kg dose of TB. 相似文献
8.
Edgard A. Ferreira Sindy V. A. Rodezno Álvaro T. Omori 《Biocatalysis and Biotransformation》2019,37(2):115-123
Porcine pancreas lipase (PPL) resolution of the α-methyl group of racemic methyl 2-methyl-4-oxopentanoate, a valuable synthetic precursor of fragrances and marine natural products, was enhanced by salt modulation of the enzymatic hydrolysis. For the enantioselective hydrolysis of the title ester, PPL was selected from a series of esterases and lipases, and its enantioselectivity was evaluated by changing the reaction medium parameters. The use of 1.6?mol L–1 sodium sulfate in phosphate buffer (pH 7.2) improved the enantioselectivity allowing the formation of methyl (2R)-(+)-2-methyl-4-oxopentanoate and (2S)-(–)-2-methyl-4-oxopentanoic acid with an enantiomeric excess of >99% and 71%, respectively. The study showed that a modulation of PPL enantioselectivity could be achieved by using kosmotropic salts in the reaction media. The present method consists of a practical and low-cost option to improve enzymatic kinetic resolution reactions. 相似文献
9.
《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1997,703(1-2)
Amlodipine, 3-ethyl 5-methyl-2-[(2-aminoethoxymethyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, is a chiral calcium antagonist, currently on the market and in therapeutic use as a racemate. The pharmacokinetic behaviour of R-(+)- and S-(−)-amlodipine after single enantiomer administration to healthy male human volunteers together with comparative administration of the racemic mixture of both enantiomers were studied. Plasma levels were studied as a function of time and assayed using an enantioselective chromatographic method (coupled chiral and achiral HPLC) with on-line solid-phase extraction and UV absorbance detection. The method was validated separately for the R-(+)- and S-(−)-enantiomer, respectively. Results of the study indicate that the pharmacokinetic behaviour of R-(+)- and S-(−)-amlodipine after single enantiomer administration is comparable to that of each enantiomer after administration of the racemate. No racemization occurs in vivo in human plasma after single enantiomer administration. 相似文献
10.
M. J. Bogusz K. D. Krüger R. D. Maier R. Erkwoh F. Tuchtenhagen 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1999,732(2):415
A selective assay of olanzapine with liquid chromatography atmospheric pressure chemical ionization (LC–APCI–MS, positive ions) is described. The drug and internal standard (ethyl derivative of olanzapine) were isolated from serum using a solid-phase extraction procedure (C18 cartridges). The separation was performed on ODS column in acetonitrile–50 mM ammonium formate buffer, pH 3.0 (25:75). After analysis of mass spectra taken in full scan mode, a selected-ion monitoring detection (SIM) was applied with the following ions: m/z 313 and 256 for olanzapine and m/z 327 and 270 for the internal standard for quantitation. The limit of quantitation was 1 μg/l, the absolute recovery was above 80% at concentration level of 10 to 100 μg/l. The method tested linear in the range from 1 to 1000 μg/l and was applied for therapeutic monitoring of olanzapine in the serum of patients receiving (Zyprexa™) and in one case of olanzapine overdose. Olanzapine in frozen serum samples and in frozen extracts was stable over at least four weeks. The examinations of urine extracts from patients receiving olanzapine revealed peaks of postulated metabolites (glucuronide and N-desmethylolanzapine). 相似文献
11.
H. Ardag Akdogan A. Demircali C. Aydemir N. Pazarlioglu F. Karci 《Applied Biochemistry and Microbiology》2011,47(5):538-542
In this study; sub-tropical white rot fungi, Trametes versicolor was investigated for its ability to degrade 4-(3′-methyl-4′-(4″-nitrophenyl)azo-1′H-pyrazol-5′-ylazo)-3-methyl-1H-pyrazol-5-on
in the mediums containing glucose and different concentrations of degrade dye in batch systems. This dye was synthetized at
Pamukkale Universtiy of Organic Chemistry research laboratory. Samples were collected on 10 days, and was detected by Shimadzu
UV-1600A spectrophotometry. Decolorization study showed that this disazo dye was removed by more than 70% in 10 days. Laccase
enzyme activity was detected in samples and then last sample was analyzed by GC-MS. Metabolites weren’t showed in GC-MS result.
It was concluded that T. versicolor could achieve the biodegradation of this new disazo dye. 相似文献
12.
Vinícius R. Campos Paula A. Abreu Helena C. Castro Carlos R. Rodrigues Alessandro K. Jordo Vitor F. Ferreira Maria C.B.V. de Souza Fernanda da C. Santos Laura A. Moura Thaisa S. Domingos Carla Carvalho Eldio F. Sanchez Andr L. Fuly Anna C. Cunha 《Bioorganic & medicinal chemistry》2009,17(21):7429-7434
The current treatment used against envenomation by Lachesis muta venom still presents several side effects. This paper describes the synthesis, pharmacological and theoretical evaluations of new 1-arylsulfonylamino-5-methyl-1H-[1,2,3]-triazole-4-carboxylic acid ethyl esters (8a–f) tested against the hemolytic profile of the L. muta snake venom. Their structures were elucidated by one- and two-dimensional NMR techniques (1H, APT, HETCOR 1JCH and nJCH, n = 2, 3) and high-resolution electrospray ionization mass spectrometry. The series of triazole derivatives significantly neutralized the hemolysis induced by L. muta crude venom presenting a dose-dependent inhibitory profile (IC50 = 30−83 μM) with 1-(4′-chlorophenylsulfonylamino)-5-methyl-1H-[1,2,3]-triazole-4-carboxylic acid ethyl ester (8e) being the most potent compound. The theoretical evaluation revealed the correlation of the antiophidian profile with the coefficient distribution and density map of the Highest Occupied Molecular Orbitals (HOMO) of these molecules. The elucidation of this new series may help on designing new and more efficient antiophidian molecules. 相似文献
13.
Raboisson P de Kock H Rosenquist A Nilsson M Salvador-Oden L Lin TI Roue N Ivanov V Wähling H Wickström K Hamelink E Edlund M Vrang L Vendeville S Van de Vreken W McGowan D Tahri A Hu L Boutton C Lenz O Delouvroy F Pille G Surleraux D Wigerinck P Samuelsson B Simmen K 《Bioorganic & medicinal chemistry letters》2008,18(17):4853-4858
SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (Ki = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics. 相似文献
14.
Motoyoshi Ohsugi Itsuo Ichimoto Hiroo Ueda 《Bioscience, biotechnology, and biochemistry》2013,77(10):1925-1928
A novel synthetic pathway to trans-4-amino-1-hydroxy-2-methyl-2-butene (7), a useful synthetic intermediate of zeatin, is presented here. On selective monophthalimide formation, the trans-1, 4-dibromo-2-methyl-2-butene (10) prepared from isoprene (1) predominantly gives trans-1-bromo-2-methyl-4-phthalimido-2-butene (11). The compound (11) is converted to 7 via trans-1-acetoxy-2-methyl-4-phthalimido-2-butene (6). The overall yield of 7 from 1 is 33.6%. Base-catalyzed hydrolysis of 11 also gives 7 directly. Zeatin can be prepared by the condensation of 7 with 6-chloropurine. 相似文献
15.
M. C. M. Roosemalen P. A. Soons T. Funaki D. D. Breimer 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1991,565(1-2)
A relatively simple reversed-phase high-performance liquid chromatographic method for the determination of the polar metabolites of nifedipine in biological fluids is described. After conversion of 2-hydroxymethyl-6-methyl-4-(2-nitrophenyl)pyridine-3,5-dicarboxylic acid 5-methyl ester (IV) into 5,7-dihydro-2-methyl-4-(2-nitrophenyl)-5-oxofuro[3,4-b]pyridine-3-carboxylic acid methyl ester (V) by heating under acidic conditions, V was extracted with n-pentane—dichloromethane (7:3) and analysed on a C18 column with ultraviolet detection. Subsequently, 2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid monomethyl ester (III) was extracted with chloroform and analysed on the same system. Limits of determination in blood were 0.1 μg/ml for III and 0.05 μg/ml for IV and V; these limits were two to ten times higher for urine. This inter-assay variability was always less than 7.5%. 相似文献
16.
Whole cells of Rhodotorula glutinis reduced N-methyl-3-oxo-3-(thiophen-2-yl) propanamide at 30 g/l to (S)-N-methyl-3-hydroxy-3-(2-thienyl) propionamide, an intermediate in the production of (S)-duloxetine, a blockbuster antidepressant drug, in 48 h. The reaction had excellent enantioselectivity (single enantiomer,
>99.5% enantiomeric excess [ee]) with a >95% conversion. 相似文献
17.
Jung Hae Yoon Gi Hyuck Ryu Paul Finch Joon Shick Rhee 《Journal of Molecular Catalysis .B, Enzymatic》2001,15(4-6)
Enzymatic synthesis of 3-O-methyl-4-O-β-
-galactopyranosyl-
-glucose (3-O-methyl-lactose) has been attempted using both galactosyltransferase and galactosidase activities. The transferase-catalysed reaction produces exclusively the desired product in β-1,4-glycosidic linkage whereas the galactosidase-catalysed reactions predominantly form a 1,6-linked disaccharide. With galactosidase, in order to change the regioselectivity, blocking of the 6-position of 3-O-methyl-
-glucose and anomeric modification of the acceptor structure were investigated. Although acetylation of the 6-position of 3-O-methyl glucose catalysed by lipase was successful, the synthesis of the desired disaccharide did not occur. 相似文献
18.
Ikeda Y Ohki S Koizumi K Tanaka A Watanabe H Kohno H van Rensen JJ Böger P Wakabayashi K 《Photosynthesis research》2003,77(1):35-43
A series of replacement experiments of [14C]-triazines, [14C]-atrazine and [7-14C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine, bound to thylakoids isolated from wild-type and atrazine-resistant
Chenopodium album (lambsquarters) were conducted. Replacement experiments of [14C]-triazines bound to wild-type Chenopodium thylakoids with non-labeled atrazine and 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine were carried out, to elucidate
whether benzylamino-1,3,5-triazines use the same binding niche as atrazine. [14C]-Atrazine and [7-14C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine bound to wild-type thylakoids were replaced by non-labeled 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine
and non-labeled atrazine, respectively. The above two replacements showed mutual competition. To clarify further whether benzylamino-1,3,5-triazines
bind at the D1-protein to amino acid residue(s) different from atrazine or not, experiments to replace [7-14C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazines bound to atrazine-resistant Chenopodium thylakoids by non-labeled atrazine, 2-(4-bromobenzylamino)-4-methyl-6-trifluoromethyl-1,3,5-triazine, DCMU and DNOC were
carried out. Although the bound [7-14C]-2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine was difficult to be replaced even with high concentrations of atrazine,
[14C]-labeled 1,3,5-triazine was competitively replaced by non-labeled 2-(4-bromobenzylamino)-4-methyl-6-trifluoromethyl-1,3,5-triazine,
DCMU or DNOC. Thus, 2-benzylamino-4-methyl-6-trifluoromethyl-1,3,5-triazine herbicides are considered to bind to the same
niche at the D1 protein as atrazine, but use amino acid residue(s) different from those involved with atrazine binding.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
19.
We have compared the effects of cycloheximide (CHI) and two other rapid and effective inhibitors of protein synthesis, pactamycin and 2-(4-methyl-2,6-dinitroanilino)-N-methyl proprionamide (MDMP), on protein synthesis, respiration, auxin-induced growth and H+-excreation of Avena sativa L. coleoptiles. All three compounds inhibit protein synthesis without affecting respiration. The effectiveness of the inhibitors against H+-excretion and growth correlates with their ability to inhibit protein synthesis. Both CHI and MDMP inhibit auxin-induced H+-excretion after a latent period of 5–8 min, and inhibit growth after a 8–10-min lag. These results support the idea that continued protein synthesis is required in the initial stages of the growth-promoting action of auxin.Abbreviations CHI
cycloheximide
- DMSO
dimethyl sulfoxide
- FC
fusicoccin
- IAA
indole-3-acetic acid
- MDMP
2-(4-methyl-2,6-dinitroanilino)-N-methyl proprionamide 相似文献
20.
Diastereoselective hydroxylation and reduction of derivatised tetrahydrofurans by
Beauveria bassiana
The filamentous fungus, Beauveria bassiana ATCC 7159, catalyses the regio- and diastereoselective biohydroxylation of trans-2-methyl-5-benzyloxymethyl-tetrahydrofuran to the cis-3-hydroxy derivative. When incubated with cis-2-methyl-3-keto-5-benzyloxymethyltetrahydrofuran, the same fungus performs a reduction to give the cis- and trans-alcohols in a 4:1 ratio. 相似文献