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31.
Ochiai H Ohtani T Ishida A Kusumi K Kato M Kohno H Odagaki Y Kishikawa K Yamamoto S Takeda H Obata T Nakai H Toda M 《Bioorganic & medicinal chemistry》2004,12(17):4645-4665
The hypothesis that the dose-limiting side effects of PDE4 inhibitors could be mediated via the central nervous system prompted us to design and synthesize a hydrophilic piperidine analog to improve the side effect profile of Ariflo 1, which is an orally active second-generation PDE4 inhibitor. During evaluation of various water-soluble piperidine analogs, 2a-b, 11b-14b, and 17a showed therapeutic potential in cross-species comparison studies. The following three findings were obtained: (1) The hydroxamic acid group, a well known metal chelator, caused a marked increase of inhibitory activity. (2) Water-soluble piperidine analogs lacked the configurational isomerism of Ariflo 1 without loss of inhibitory activity. (3) Replacement of the 4-methoxy residue with a difluoromethoxy residue led to an increase of in vivo potency. Structure-activity relationships are presented. Single-dose rat pharmacokinetic data for 11b, 12b, and 17a are also presented. 相似文献
32.
Atushi Ushimaru Satoshi Kikuchi Ryuji Yonekura Atsushi Maruyama Nao Yanagisawa Maiko Kagami Michiko Nakagawa Suzuki Mahoro Yukihiko Kohmatsu Aya Hatada Shumpei Kitamura Kensuke Nakata 《Nordic Journal of Botany》2004,24(5):593-598
We compared the amount of variation in flower size between autogamous and insect-pollinated species to examine the hypothesis that pollinator-mediated selection stabilizes flower size in plant populations. One would expect the flower size variation to be larger in selfing species that are less affected by pollinator-mediated stabilizing selection than in insect-pollinated species. The results of phylogenetic comparisons between autogamous and insect-pollinated flowers supported the pollinator-mediated stabilizing selection hypothesis, although the non-phylogenetic comparison did not. According to our results, we discuss the factors influencing the flower size variation. 相似文献
33.
Araki K Takakura H Miyajima Y Akashi Y Kawanishi K Kakita S Kondo Y 《The Journal of General and Applied Microbiology》1999,45(4):169-176
During a study on the effect of DL-serine hydroxamate on Corynebacterium glutamicum (JCM1318, a wild strain), a mutant resistant to the drug, strain TO3002, was isolated. This mutant accumulated five Ehrlich's reagent positive fluorescent substances in the culture medium. Two major and one minor fluorescent products were isolated by preparative high-performance liquid chromatography following charcoal column chromatography from the culture supernatant. One major product was identified as anthranilic acid whose molecular ion was confirmed to be 137 by a measurement of liquid chromatography-mass spectrometry (LC-MS), and NMR spectrum coincided with that of anthranilic acid. LC-MS spectra of another major and the minor product showed that they had the same molecular weight of 299. This major product was supported to be N-glucosylanthranilic acid (N-o-carboxyphenyl-1-beta-glucosylamine) by two-dimensional (1)H and (13)C NMR analyses. The minor product was speculated to be an Amadori compound derived from N-glucosylanthranilic acid. N-Glucosylanthranilic acid accumulated in the early phase, then decreased in the late phase of the culture. In contrast, the accumulation of anthranilic acid increased remarkably in the late phase of the fermentation. Based on this phenomenon, it was assumed that N-glucosylanthranilic acid once accumulated was decomposed to form anthranilic acid, at least in large part, with the progress of fermentation. The strain TO3002 showed a leaky requirement for L-tryptophan or indole (but did not for anthranilic acid) and resistance to DL-serine hydroxamate. 相似文献
34.
Hattori S Kawaharada C Tazaki H Fujimori T Kimura K Ohnishi M Nabeta K 《Bioscience, biotechnology, and biochemistry》2004,68(12):2656-2659
Thermally decomposed products of (+/-)-linalyl beta-D-glucoside were analyzed by GC and GC/MS. 2,6-dimethyl-2,6-octadienes produced by mild pyrolysis of linalyl beta-D-glucopyranoside under a vacuum were detected and characterized by MS and NMR spectroscopy. This suggests that 2,6-dimethyl-2,6-octadienes are produced during thermal decomposition of the glucoside via proton transfer from the anomeric position to C-6 in the aglycon moiety. A stable isotope labeling experiment directly indicated the new reaction mechanism. 相似文献
35.
Effects of soybean beta-conglycinin on hepatic lipid metabolism and fecal lipid excretion in normal adult rats 总被引:1,自引:0,他引:1
Fukui K Kojima M Tachibana N Kohno M Takamatsu K Hirotsuka M Kito M 《Bioscience, biotechnology, and biochemistry》2004,68(5):1153-1155
beta-Conglycinin decreased blood triacylglycerol (TAG) levels in male Wistar adult rats. Liver mitochondrial carnitine palmitoyltransferase activity in the beta-conglycinin-fed group significantly increased as against the casein-fed group. Hepatic fatty acid synthase activity in the beta-conglycinin group significantly decreased as against that of the casein-fed group. Fecal fatty acid excretion in the beta-conglycinin group was significantly higher than in the casein group. 相似文献
36.
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38.
Ochiai H Ohtani T Ishida A Kusumi K Kato M Kohno H Kishikawa K Obata T Nakai H Toda M 《Bioorganic & medicinal chemistry letters》2004,14(1):207-210
Based on the hypothesis that the dose-limiting side effects of PDE4 inhibitors could be mediated via the central nervous system (CNS), design and synthesis of a hydrophilic analogue is considered to be one approach to improving the side-effect profile of Ariflo 1. Water-soluble piperidine derivatives were found to possess therapeutic potential. 相似文献
39.
Kobayashi N Takahashi K Takayanagi K Takahashi K Masuko S Tadano T Kisara K Kinemuchi H 《Life sciences》2002,70(13):1519-1531
Various mammalian tissues contain a tissue-bound amine oxidizing enzyme distinct from mitochondrial outer membrane enzyme, monoamine oxidase (MAO, EC 1.4.3.4), termed semicarbazide-sensitive amine oxidase (SSAO, EC 1.4.3.6). An increase in SSAO activity was found in patients suffering from vascular disorders such as diabetes and diabetic complications. It has previously been shown that 2-bromoethylamine (2-BEA) is a potent, and selective suicidal inhibitor of tissue-bound SSAO. The aim of this study was to investigate the interaction of this suicidal SSAO inhibitor with the tissue-bound enzyme in guinea pig lung, kidney, stomach, and heart homogenates. The conditions necessary for this inhibitor to titrate the concentrations of this enzyme were also determined. 2-BEA appears to interact with SSAO, as reported previously for this enzyme from different sources, in a manner consistent with an irreversible, "suicide" reaction. Because of this property, 2-BEA could be used to titrate the concentrations of SSAO active centers in these tissues under the appropriate conditions employed. Although some possible non-specific binding of the inhibitor to sites other than the active center of the enzyme, metabolism of this inhibitor and/or presence of enzyme subtypes was hypothesized, the molecular characteristics of SSAO in these tissues (Km, Vmax values, enzyme efficiencies, approximate enzyme concentrations, and molecular turnover numbers) towards the substrate kynuramine (0.1 mM) at pH 7.4 and 37 degrees C have been estimated. 相似文献
40.
Measurement of cerebral oxygenation in neonates after vaginal delivery and cesarean section using full-spectrum near infrared spectroscopy 总被引:5,自引:0,他引:5
Isobe K Kusaka T Fujikawa Y Okubo K Nagano K Yasuda S Kondo M Itoh S Hirao K Onishi S 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2002,132(1):133-138
To investigate whether or not the mode of delivery produces differences in cerebral oxygenation, cerebral hemoglobin oxygen saturation was measured using full-spectrum near infrared spectroscopy in 26 healthy term newborn infants immediately after birth. Infants in group 1 (n=20) were delivered vaginally, and those in group 2 (n=6) by elective cesarean section. Arterial oxygen saturation in the right hand was also measured simultaneously using a pulse oximeter. Changes in arterial oxygen saturation showed no significant difference between the two groups. The mean+/-S.D. of cerebral hemoglobin oxygen saturation in group 1 increased rapidly after birth, from 29+/-17% at 2 min to 68+/-6% at 8.5 min, followed by an almost constant value (66+/-7% at 15 min). In comparison, cerebral hemoglobin oxygen saturation in group 2 also increased rapidly until 8.5 min, but after this time decreased significantly to 57+/-5% at 15 min after birth. This indicates that the mode of delivery has a marked influence on cerebral oxygenation immediately after birth. 相似文献