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991.
Kuramochi T Kakefuda A Yamada H Sato I Taguchi T Sakamoto S 《Bioorganic & medicinal chemistry》2004,12(19):5039-5056
The sodium-calcium exchanger (NCX) is known as the transporter that controls the concentration of Ca(2+) in cardiac myocytes. In the setting of heart failure and myocardial ischemia-reperfusion, NCX underlies an arrhythmogenic transient inward current responsible for delayed after--depolarizations and nonreentrant initiation of ventricular tachycardia. NCX is an attractive target for treatment in heart failure and myocardial ischemia-reperfusion. We have designed and synthesized a series of phenoxypyridine derivatives, based on compound 3. These derivatives have been evaluated for their inhibitory activity against both the reverse and forward mode of NCX in CCL39 cells. We have discovered several novel potent NCX inhibitors (39q, 48k), which have a high selectivity for reverse NCX inhibitory activity. 相似文献
992.
Koshio H Hirayama F Ishihara T Kaizawa H Shigenaga T Taniuchi Y Sato K Moritani Y Iwatsuki Y Uemura T Kaku S Kawasaki T Matsumoto Y Sakamoto S Tsukamoto S 《Bioorganic & medicinal chemistry》2004,12(20):5415-5426
Factor Xa (fXa) is a serine protease, which plays a pivotal role in the coagulation cascade. To improve the oral anticoagulant activity of fXa inhibitors containing a 1,4-diazepane moiety as the P4 part, a prodrug strategy was examined. Among the compounds evaluated in this study, amidoxime prodrugs bearing an ester moiety, such as compounds 21 and 30, showed effective oral anticoagulant activity in mice. 相似文献
993.
Otx genes are expressed in the anterior neural tube and endoderm in all of the chordates so far examined. In mouse embryos, important roles of otx genes in the brain development have been well documented. However, roles of otx genes in other chordate species have been less characterized. To advance our understanding about roles of otx genes in chordates, we have studied Hroth, otx of the ascidian, Halocynthia roretzi. Hroth is expressed in the anterior part of the neural tube (the sensory vesicle), the endoderm and anterior epidermis in the development. In this study, we investigated roles of Hroth in the larval development through an antisense morpholino oligonucleotides (MOs) approach. Embryos injected with Hroth-targeting MO (Hroth knockdown embryos) developed into larvae without the adhesive organ, sensory pigment cells and cavity of the sensory vesicle. The tissues, in which defects were observed, are derived from anterior-animal cells of the embryo in early cleavage stages. During cleavage stages, Hroth is also expressed in the endoderm precursors of the vegetal hemisphere. However, Hroth expression in the anterior endoderm precursors do not seem to be essential for the above defects, since MO injection into the anterior-animal but not anterior-vegetal pair cells at the 8-cell stage gave the defects. Analysis of marker gene expression demonstrated that the fate choice of the sensory vesicle precursors and the specification of the sensory vesicle territory occurred normally, but the subsequent differentiation of the sensory vesicle was severely affected in Hroth knockdown embryos. The anterior trunk epidermis including the adhesive organ-forming region was also affected, indicating that anterior epidermal patterning requires Hroth function. Based on these findings, similarities and differences in the roles of otx genes between ascidians and mice are discussed. 相似文献
994.
Studies on anti-Helicobacter pylori agents. Part 3: A novel, efficacious cephem derivative, FR193879
Yoshida Y Matsuda K Sasaki H Matsumoto Y Matsumoto S Tawara S Takasugi H 《Bioorganic & medicinal chemistry letters》2004,14(10):2627-2631
The synthesis, therapeutic efficacy against H. pylori, and preliminary safety of the novel cephem derivative, FR193879 (8a) are described. Compound 8a having a (4-carbamoylmethylthiazol-2-yl)thio moiety at the 3-position and a phenylacetamido at the 7-position was found to have good safety showing a nontoxic dose of > 100 mg/kg in dogs in a 4-week repeat dose toxicity study and extremely potent therapeutic efficacy against H. pylori, showing 30 times superior activity compared to AMPC, and did not display cross-resistance with CAM or MNZ. 相似文献
995.
Torisu K Kobayashi K Iwahashi M Nakai Y Onoda T Nagase T Sugimoto I Okada Y Matsumoto R Nanbu F Ohuchida S Nakai H Toda M 《Bioorganic & medicinal chemistry letters》2004,14(19):4891-4895
A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and evaluated for prostaglandin D(2) (DP) receptor affinity and antagonist activity. Some of them exhibited strong receptor binding and were potent in the cAMP formation assays. These antagonists also suppressed allergic inflammatory responses such as the PGD(2)-induced increase of microvascular permeability. Structure-activity relationship (SAR) data are presented. 相似文献
996.
Watanabe M Asatsuma M Ikui A Ikeda M Yamada Y Nomura S Igarashi A 《Chemical senses》2005,30(2):121-125
We have measured and compared several metallic elements and matrix metalloproteinases (MMPs) in saliva from patients with taste disorder and healthy subjects. Stimulated whole saliva was collected from 20 patients and 35 healthy subjects. Inductively coupled plasma mass spectrometry (ICP-MS) was used for the determination of metallic elements in saliva. Amounts of MMP-1, MMP-3, MMP-9 and IL-1alpha, IL-6 in saliva were measured using an enzyme-linked immunosorbent assay systems. Zinc in the serum was determined by flame atomic absorption spectrometry. Our results provide evidence that levels of zinc, manganese and the amount of MMP-3 in saliva are significantly decreased in the patients with taste disorder compared to the healthy subjects; Zn (p.p.b.): healthy subjects 79.8 +/- 42.6, patients 47.22 +/- 17.1, (P < 0.001), Mn (p.p.b.): healthy subjects 4.48 +/- 2.46, patients 2.78 +/- 1.23, (P < 0.004), MMP-3 (ng/ml), healthy subjects 0.820 +/- 0.417, patients 0.594 +/- 0.179 (P < 0.01). In contrast, copper is significantly increased in the patients; Cu (p.p.b.): healthy subjects 34.5 +/- 13.5, patients 45.9 +/- 20.8 (P < 0.049). These differences may be closely related with this disease. ICP-MS is an easy and accurate instrument for measurements of salivary metallic elements and may be useful in establishing a diagnosis of taste disorder. 相似文献
997.
p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease 总被引:19,自引:0,他引:19
Bae BI Xu H Igarashi S Fujimuro M Agrawal N Taya Y Hayward SD Moran TH Montell C Ross CA Snyder SH Sawa A 《Neuron》2005,47(1):29-41
998.
We report the discovery of a mutualistic system encompassing prey–predator interactions. A domatium is a small space in a vein axil on the underside of leaves of woody angiosperms. Cinnamomum camphora Linn. has domatia that harbor a microphytophagous eriophyid mite (sp. 1). We previously reported that a predatory mite, Euseius sojaensis (Ehara), depends on this eriophyid mite as food. We revealed that E. sojaensis also preyed upon another eriophyid mite (sp. 2) that induces galls on leaves, and that the mean area of C. camphora leaves with galls was usually less than half that of leaves without galls. We experimentally tested the effect of E. sojaensis on galls, and confirmed that the presence of E. sojaensis reduced gall induction. Therefore, C. camphora, eriophyid mite sp. 1, and E. sojaensis comprise a mutualistic system, in spite of the prey–predator interactions among them. The conventional concept of mutualism does not apply to such prey–predator interactions, so we defined them as systematic mutualism. Here, the system consists of three trophic levels, and individuals that constitute this system benefit from the other species that constitute this system. 相似文献
999.
Honda N Inaba M Katagiri T Shoji S Sato H Homma T Osaka T Saito M Mizuno J Wada Y 《Biosensors & bioelectronics》2005,20(11):2306-2309
To realize highly sensitive electrochemical immunoassays, a micro-fabricated three-dimensional (3D) electrode was fabricated and applied to enzyme immuno assay based on production of a redox species. The dimensions of the electrodes are 10 microm in width and 30 microm in height, with 20 microm spacing in between, and the 30 pairs of anode and cathode electrodes made up a single sensor. This structure lead to enhancement of the electrochemical reaction, nearly 100% of trap ratio of redox species. It can be applied to highly sensitive enzyme immuno sensing based on p-aminophenylphosphate (PAPP). Applicability of this technique to the immuno assay for one of the clinical diagnostic marker proteins (alpha-fetoprotein; AFP) from 6 to 500 ng/mL was demonstrated. 相似文献
1000.
Suzuki A Hasegawa M Ishii M Matsumura S Toshima K 《Bioorganic & medicinal chemistry letters》2005,15(20):4624-4627
Certain anthraquinones, which are present in many biologically important natural products, effectively and randomly cleaved proteins (BSA or Lyso) during photoirradiation using a long wavelength UV light without any further additives. It was also found that this ability could be improved by the attachment of a suitable substituent into the anthraquinone core skeleton. 相似文献