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排序方式: 共有1162条查询结果,搜索用时 343 毫秒
1.
Steffen Vojacek Lukas Schulig Nathalie Wössner Norman Geist Prof. Dr. Walter Langel Prof. Dr. Manfred Jung Prof. Dr. Dennis Schade Prof. Dr. Andreas Link 《ChemMedChem》2019,14(8):853-864
Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp3 hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC50 value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling. 相似文献
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Oxidation behavior of a 2 mol % divinylbenzene (DVB)‐crosslinked polystyrene‐supported permanganate function was investigated toward low molecular weight primary and secondary alcohols and aldehydes. The permanganate function was attached to a polystyrene support through cyclic polyoxyethylene (POE) units immobilized on the support. Contrary to the oxidations catalyzed by low molecular weight permanganate reagents, the oxidation of primary alcohol terminated in the aldehyde stage. The secondary alcohols were converted to the respective ketone and aldehyde to acid. The effect of the variable parameters similar to solvent, temperature, and reagent to substrate ratio was followed. Nonpolar cyclohexane was found to be the best solvent for the present study. Also the reactivity increased with increasing temperature. The oxidizing reagent possesses a long shelf life and could be recycled several times without reduction of capacity and mechanical stability. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3708–3717, 2003 相似文献
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Quantitation of Cefaclor in Pharmaceutical Dosage Forms Using High Performance Liquid Chromatography
Mary Mathew V. Das Gupta Charlie Bethea 《Drug development and industrial pharmacy》1993,19(14):1723-1729
A stability-indicating high-performance liquid chromatography for the quantitation of cefaclor in pharmaceutical dosage forms has been developed. The method is accurate and precise with a percent relative standard deviation of 1.2 based on 5 readings. A number of inactive ingredients present in the capsules and suspensions did not interfere with the assay procedure. The extraction procedure from the dosage forms is very simple. The recovery from the synthetic mixtures was quantitative. The capsules which had expired 3 years ago lost only 3% of the potency. The drug appears to be very sensitive to strong acids or bases since a 5 minute boiling caused 100% degradation of drug in both the solutions. 相似文献
5.
Hsu S. Alvandpour A. Mathew S. Shih-Lien Lu Krishnamurthy R.K. Borkar S. 《Solid-State Circuits, IEEE Journal of》2003,38(5):755-761
This paper describes a 32-KB two-read, one-write ported L0 cache for 4.5-GHz operation in 1.2-V 130-nm dual-V/sub TH/ CMOS technology. The local bitline uses a leakage-tolerant self reverse-bias (SRB) scheme with nMOS source-follower pullup access transistors, while preserving robust full-swing operation. Gate-source underdrive of -220 mV on the bitline read-select transistors is established without external bias voltages or gate-oxide overstress. Device-level measurements in the 130-nm technology show 72/spl times/ bitline active leakage reduction, enabling low-V/sub TH/ usage, 40% bitline keeper downsizing, and 16 bitcells/bitline. 11% faster read delay and 2/spl times/ higher dc noise robustness are achieved compared with high-performance dual-V/sub TH/ bitline scheme. Sustained performance and robustness benefits of the SRB technique against conventional dynamic bitline with scaling to 100- and 70-nm technology is also presented. 相似文献
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Vulcanization of latex products are usually carried out at lower temperatures compared to dry rubber products. It has been suggested that, in latex vulcanization systems where thiourea is used as a secondary accelerator, it acts as a nucleophilic reagent facilitating the cleavage of the sulfur bonds in the primary accelerator like TMTD or CBS at lower temperature. But no conclusive proof is given to such a postulate. In the present study 1-phenyl-2,4-thiobiuret (DTB II) and 1,5-diphenyl-2,4-dithiobiuret (DTB III), which are more nucleophilic than thiourea and which vary in their nucleophilic reactivity, were studied as secondary accelerators along with tetramethyl thiuram disulphide (TMTD) and N-cyclohexylbenzothiazyl sulphenamide (CBS) in the vulcanization of natural rubber latex. These binary systems were found to be very effective in reducing the optimum vulcanization time. Also it was noted that 1-phenyl-2,4-dithiobiuret, which is more nucleophilic, is more reactive (as observed from the reduction in optimum cure time) as a secondary accelerator, indicating a nucleophilic reaction mechanism in the vulcanization reactions under review. The optimum dosages of the secondary accelerators required were derived. Physical properties like tensile strength, 300% modulus, and elongation at break of the latex vulcanizates were also studied. There is a definite advantage with respect to many of these properties for dithiobiuret systems compared to the systems containing TMTD alone or TMTD/thiourea. DTB III gives higher values in many of these physical properties than DTB II. Chemical characterization of the vulcanizates was also carried out to correlate the physical properties with the type of chemical crosslinks formed. © 1993 John Wiley & Sons, Inc. 相似文献
9.
BACKGROUND: The results of palliative chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in patients with advanced breast cancer who received adjuvant therapy with the same regimen were investigated. RESULTS: Of 47 patients, 14 (30%) achieved an objective remission (median duration 9.5, range 5-21 months) and 8 (17%) stabilisation of disease (median duration 6, range 3-17 months). Objective remissions were observed in premenopausal as well as in postmenopausal women, in patients with all categories of dominant localisation of disease and regardless of the oestradiol receptor status of the primary tumour or eventual previous endocrine therapy. One of 4 and 13 of 43 patients who started palliative chemotherapy within or later than 12 months after the last adjuvant course obtained an objective remission. The median survival time from start of therapy of all treated patients was 12 (range 1-40) months. Patients with an objective remission or stable disease and patients with progressive disease had a median survival time of 20 (range 6-40) and 6 (range 1-35) months respectively (p < 0.0001). CONCLUSIONS: Palliative treatment with CMF should not be rejected for patients who have relapsed after adjuvant chemotherapy with the same modality. 相似文献
10.
SA Whitmore C Settasatian J Crawford KM Lower B McCallum R Seshadri CJ Cornelisse EW Moerland AM Cleton-Jansen AJ Tipping CG Mathew M Savnio A Savoia P Verlander AD Auerbach C Van Berkel JC Pronk NA Doggett DF Callen 《Canadian Metallurgical Quarterly》1998,52(3):325-331
BACKGROUND: Both fibroblast-mediated cytokine gene therapy and bone marrow transplantation (BMT) have proven to be efficient protocols for the recovery of bone marrow depression. In this report, the effects of fibroblast-mediated interleukin (IL)-6 gene therapy, in combination with BMT, on the recovery of irradiation-induced bone marrow depression were investigated. METHODS: NIH3T3 fibroblast cells engineered to secrete IL-6 (NIH3T3-IL-6) or NIH3T3 cells transduced with the neomycin gene (NIH3T3-Neo), in combination with 10(7), 10(6), or 10(5) syngeneic bone marrow cells, were implanted into irradiated mice. RESULTS: The platelets and white blood cells in the peripheral blood of the irradiated mice increased greatly 12 days after implantation of NIH3T3-IL-6 cells and BMT, the white blood cell counts were restored to a normal level 32 days after the combined therapy, and the platelet number was obviously higher than that in mice implanted with NIH3T3-Neo and BMT. Twenty and 25 days after the combined therapy, the mice showed accelerated recovery of colony-forming unit (CFU)-granulocyte/macrophages and CFU-megakaryocytes when compared with the mice implanted with NIH3T3-Neo cells and BMT. Ten days after lethal irradiation with gamma rays, the spleens formed more CFU-spleen in mice implanted with NIH3T3-IL-6 cells and BMT than in mice injected with phosphate-buffered saline or NIH3T3-Neo cells. Combined therapy with NIH3T3-IL-6 cell implantation and BMT delayed the survival period of the hematopoietic-depressed mice significantly when compared with therapy with NIH3T3-Neo cell implantation and BMT. CONCLUSIONS: These data demonstrated that the combined therapy of fibroblast-mediated IL-6 gene therapy and BMT could significantly promote the recovery of irradiation-induced hematopoietic depression. 相似文献