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21.
Ronghui Lin Larry E. Weaner 《Journal of labelled compounds & radiopharmaceuticals》2012,55(8):296-299
Synthesis of multiple stable isotope‐labeled antibacterial agent RWJ‐416457, (N‐{3‐[3‐fluoro‐4‐(2‐methyl‐2,6‐dihydro‐4H‐pyrrolo[3,4‐c]pyrazol‐5‐yl)‐phenyl]‐2‐oxo‐oxazolidin‐5‐ylmethyl}‐acetamide), and its major metabolite, N‐{3‐[4‐(2,6‐dihydro‐4H‐pyrrolo[3,4‐c]pyrazol‐5‐yl)‐3‐fluoro‐phenyl]‐2‐oxo‐oxazolidin‐5‐ylmethyl}‐acetamide, is described. The stable isotope‐labeled [13CD3]RWJ‐416457 was prepared readily by acetylation of the precursor amine, 5‐aminomethyl‐3‐[3‐fluoro‐4‐(2‐methyl‐2,6‐dihydro‐4H‐pyrrolo[3,4‐c]pyrazol‐5‐yl)‐phenyl]‐oxazolidin‐2‐one with CD313COCl in pyridine. Synthesis of the stable isotope‐labeled metabolite involved a construction of multiple isotope‐labeled pyrazole ring. N,N‐dimethyl(formyl‐13C,D)amide dimethyl acetal was first prepared by treating N,N‐dimethyl(formyl‐13C,D)amide with dimethyl sulfate, followed by sodium methoxide. Then, N‐{3‐[3‐fluoro‐4‐(3‐oxo‐pyrrolidin‐1‐yl)‐phenyl]‐2‐oxo‐oxazolidin‐5‐ylmethyl}‐acetamide was condensed with N,N‐dimethyl(formyl‐13C,D)amide dimethyl acetal, and the resultant β‐ketoenamine intermediate underwent pyrazole ring formation with hydrazine‐15N2, to give the [13C15N2D]‐labeled metabolite. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
22.
M.Clara Sañudo-Peña Kang Tsou Eugene R Delay Andrea G Hohman Michelle Force J.Michael Walker 《Neuroscience letters》1997,223(2):33
Human use of marijuana (Cannabis sativa) is widely assumed to have rewarding properties, a notion supported by its widespread recreational use. However, no study has clearly demonstrated such effects in animal models. The purpose of this study was to test for the presumed rewarding effect of cannabinoids using a conditioned place preference paradigm. The results showed that animals failed to develop place conditioning at a low dose (1.5 mg/kg) and developed a place aversion at a high dose (15 mg/kg) of the active principle in marijuana, Δ9-tetrahydrocannabinol (Δ9-THC), a finding consistent with most previous studies. Moreover, the administration of the cannabinoid antagonist SR141716A induced a conditioned place preference at both a low (0.5 mg/kg) and a high (5 mg/kg) dose. In summary, cannabinoid antagonism produced place preference while cannabinoid agonism induced place aversion. These results suggest that endogenous cannabinoids serve normally to suppress reward or to induce aversion. 相似文献
23.
24.
Pinna GA Pirisi MA Mussinu JM Murineddu G Loriga G Pau A Grella GE 《Il Farmaco; edizione pratica》2003,58(9):749-763
Tricyclic pyrazole dimers that comprise two kinds of CONH-(CH(2))(n)-N(CH(3))-(CH(2))(n)-NHCO bridges to which are linked potential DNA-intercalating groups such as 1H-benzo[g]indazole, 2H-benzo[g]indazole and 1,4-dihydroindeno[1,2-c]pyrazole were designed, synthesized and some of them evaluated in vitro by NCI (Bethesda, USA) against nine types of cancer cells. Compounds 2a, 2f-i and 2o-r demonstrated significant antiproliferative activity, all with GI(50) values in the low micromolar range. Preliminary analysis of the structure-activity relationship for dimers 2 indicated that: (i) in the ground terms (2a and 2k) antitumor activities were strongly related to the type of chromophore, (ii) in contrast, either 1H-benzo[g]indazole- or 1,4-dihydroindeno[1,2-c]pyrazole-dimers when bore a N(1)-aryl group (2g, 2h, 2i, 2o, 2p, 2q and 2r) generally showed a good level of antitumor potency and (iii) for the most representative compounds (pairs of compounds: 2g,2h; 2o,2p and 2q,2r) the length of the bridges did not significantly contribute to the variations in cytotoxicity. Two members of this series, 2f and 2q, were selected and tested in the hollow fiber cell assay to evaluate in a preliminary fashion their in vivo antitumor activity. Finally, viscosity measurement of 2f with poly(dA-dT)(2), confirmed that these promising compounds behaved as typical DNA-intercalating agents. 相似文献
25.
M Moriya T Ohta K Watanabe Y Watanabe F Sugiyama T Miyazawa Y Shirasu 《Cancer letters》1979,7(6):325-330
Inhibitory effects of several chemicals on the mutagenicities of 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM) for Salmonella typhimurium G46 in the host-mediated assay were investigated. They were carbon disulfide (CS2), tetraethylthiuram disulfide (disulfiram, DSF), sodium diethyldithiocarbamate (SDDC), ethylene-bis(dithiocarbamato) manganese (Maneb), pyrazole (PZ), aminoacetonitrile hydrogen sulfate (AAN), and sodium selenite (SE). All the compounds, except for SE, inhibited the mutagenicities of DMH and AOM. 相似文献
26.
Seven new 2-(3-(4-aryl)-1-phenyl-1H-pyrazol-4-yl) chroman-4-ones (4a-4g) have been synthesized by cyclization of 2-hydroxychalcone analogues of pyrazole 3a-3g using conc. HCl in acetic acid. The structures of the compounds 4a-4g were established by the combined use of (1)HNMR, IR and mass spectra. All the seven compounds were tested in vitro for their antibacterial activity against two Gram positive bacteria namely Staphylococcus aureus and Bacillus subtilis and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The compounds 4b, 4c, 4e, 4f, 4g have displayed good antibacterial activity when compared with commercially available antibiotic, ciprofloxacin. These compounds also were screened for their antifungal activity against two ear pathogenic fungi, namely Aspergillus Niger and A. flavus. The compounds 4a, 4c, 4d, 4g exhibited good antifungal activity when compared with commercially available antifungal, fluconazole. 相似文献
27.
以(±)-13β,17α-二乙基-17β-羟基-5α-甾烷-3-酮(Ⅱ)为原料,经甲酰化、缩合反应合成了(±)-13β,17α,-二乙基-17β-羟基-5α-甾烷骈[3,2-C]吡唑(Ⅴ);又将甲酰化反应所得羟次甲基化合物(Ⅳ)依次转变成单肟(Ⅵ)、双肟(Ⅶ)、再坏合成(±)-13β,17α-二乙基-5α-甾烷骈[2,3-C]呋咱(Ⅷ)。 采用类似的反应,从(Ⅱ)及(Ⅳ)的5β-异构体(Ⅲ)和(Ⅸ)分别合成了(±)-13β,17α-二乙基-17β-羟基-5β-甾烷骈[3,2-C]吡唑(Ⅹ)与(±)-13β,17α-二乙基-17β-羟基-5β-甾烷骈[2,3-C)呋咱(ⅩⅢ)。 相似文献
28.
以(±)-13β,17α-二乙基-17β-羟基-5α-甾烷-3-酮(Ⅱ)为原料,经甲酰化、缩合反应合成了(±)-13β,17α,-二乙基-17β-羟基-5α-甾烷骈[3,2-C]吡唑(Ⅴ);又将甲酰化反应所得羟次甲基化合物(Ⅳ)依次转变成单肟(Ⅵ)、双肟(Ⅶ)、再坏合成(±)-13β,17α-二乙基-5α-甾烷骈[2,3-C]呋咱(Ⅷ)。采用类似的反应,从(Ⅱ)及(Ⅳ)的5β-异构体(Ⅲ)和(Ⅸ)分别合成了(±)-13β,17α-二乙基-17β-羟基-5β-甾烷骈[3,2-C]吡唑(Ⅹ)与(±)-13β,17α-二乙基-17β-羟基-5β-甾烷骈[2,3-C)呋咱(ⅩⅢ)。 相似文献
29.
Ten new 1-thiocarbamoyl-3-(phenyl and/or 4-substituted phenyl)-5-(3,4-dimethoxyphenyl and/or 2-chloro-3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole derivatives were synthesized by reacting 1,3-diphenylpropen-1-ones and thiosemicarbazide. The chemical structures of the compounds were verified by means of their IR, 1H-NMR, ESI-MS spectroscopic data and elementary analyses. All the compounds were investigated for their ability to selectively inhibit monoamine oxidase (MAO) by in-vitro tests. Monoamine oxidase was isolated and purified from the mitochondrial extracts of rat-liver homogenates and human platelets. Monoamine oxidase inhibitory activities of the compounds were compared with pargyline and clorgyline. Most of the compounds inhibited the total activity of rat liver homogenates. The monoamine oxidase-A inhibitory effects of 1-thiocarbamoyl-3-(4-methoxyphenyl)-5-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1-thiocarbamoyl-3-(4-methoxyphenyl)-5-(2-chloro-3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole were detected as potent as clorgyline. Selective and irreversible inhibition of rat liver monoamine oxidase-A by synthesized compounds have promising features for designing the new selective monoamine oxidase A inhibitors as potent and reliable anti-depressants in the future. 相似文献
30.
Methanol poisoning 总被引:1,自引:0,他引:1
C E Becker 《The Journal of emergency medicine》1983,1(1):51-58
Methanol poisoning is an uncommon but an extremely hazardous intoxication. Since methanol is a versatile fuel and is having increasing usage in an energy-conscious society, a high index of suspicion and swift laboratory confirmation is essential in managing this poisoning. Methanol poisoning may occur in sporadic or epidemic circumstances. Chronic exposure may occur in the occupational setting. Man is uniquely susceptible to methanol toxicity, perhaps dependent upon folate metabolism. Classic symptoms of methanol toxicity can only occur in laboratory animals who are rendered folate deficient. Folate may be useful in humans enhancing removal of the toxic products of methanol poisoning. The enzyme responsible for metabolism of methanol is alcohol dehydrogenase. Ethanol has a higher affinity for this enzyme and is preferentially metabolized. Simultaneous ethanol and methanol administration may confuse the onset of the intoxication. Pyrazoles may also be used to inhibit alcohol dehydrogenase thus preventing the intoxication. The most important initial symptom of methanol poisoning is visual disturbance. The symptoms may be delayed up to 24 hours after ingestion due to simultaneous alcohol administration and metabolic processes. Laboratory evidence of severe metabolic acidosis with increased anion and osmolar gaps strongly suggest the clinical diagnosis. There may be an important association between mean corpuscular volume which is significantly higher in cases of severe methanol poisoning than in mild cases.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献