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排序方式: 共有329条查询结果,搜索用时 156 毫秒
81.
Chiral Resolution and Pharmacological Characterization of the Enantiomers of the Hsp90 Inhibitor 2‐Amino‐7‐[4‐fluoro‐2‐(3‐pyridyl)phenyl]‐4‐methyl‐7,8‐dihydro‐6H‐quinazolin‐5‐one Oxime
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Dr. Raffaella Amici Dr. Chiara Bigogno Dr. Roberto Boggio Dr. Andrea Colombo Dr. Stephen M. Courtney Dr. Roberto Dal Zuffo Dr. Giulio Dondio Dr. Fulvia Fusar Dr. Stefania Gagliardi Prof. Dr. Saverio Minucci Dr. Marco Molteni Dr. Christian A. G. N. Montalbetti Dr. Annalisa Mortoni Dr. Mario Varasi Dr. Stefania Vultaggio Dr. Ciro Mercurio 《ChemMedChem》2014,9(7):1574-1585
Heat‐shock protein 90 (Hsp90) is a molecular chaperone involved in the stabilization of key oncogenic signaling proteins, and therefore, inhibition of Hsp90 represents a new strategy in cancer therapy. 2‐Amino‐7‐[4‐fluoro‐2‐(3‐pyridyl)phenyl]‐4‐methyl‐7,8‐dihydro‐6H‐quinazolin‐5‐one oxime is a racemic Hsp90 inhibitor that targets the N‐terminal adenosine triphosphatase site. We developed a method to resolve the enantiomers and evaluated their inhibitory activity on Hsp90 and the consequent antitumor effects. The (S) stereoisomer emerged as a potent Hsp90 inhibitor in biochemical and cellular assays. In addition, this enantiomer exhibited high oral bioavailability in mice and excellent antitumor activity in two different human cancer xenograft models. 相似文献
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83.
Bartolo Gabriele Lucia Veltri Giuseppe Salerno Raffaella Mancuso Mirco Costa 《Advanced Synthesis \u0026amp; Catalysis》2010,352(18):3355-3363
A novel multicomponent cascade process is reported, based on the sequential combination between an initial nucleophilic attack step to an imine moiety and a palladium‐catalyzed oxidative heterocyclization‐alkoxycarbonylation process. By this new process, five simple molecules [2‐alkynylaniline imines, alcohol (ROH), carbon monoxide (CO), alcohol (ROH), and oxygen (O2)] are sequentially activated, selectively leading to high value‐added functionalized indole derivatives in a single operation. 相似文献
84.
The efficiency of heating systems is increasingly important because of the increasing need to save energy and protect the environment. This paper presents an innovative technique for modeling multi-zone hydronic heating systems in buildings in an easier and more user friendly manner. An original approach is described in which the thermal and hydronic systems are solved simultaneously by simulating the dynamic behavior of pipe water flow rates, water temperatures, and room air temperatures. The simulation uses mathematical models that apply a Newton-Raphson method (NRM) developed in Matlab© and Simulink© environments. A user friendly graphical user interface (GUI) enables the designer to analyze any multi-zone hydronic heating system from the point of view of improving its efficiency.A laboratory heating system was used to validate this modeling technique. A series of trials were conducted in a multi-zone laboratory heating system located within the R&D division of a leading Italian boiler manufacturer, and the results presented in this paper validate the model. 相似文献
85.
De Luca S Saviano M Della Moglie R Digilio G Bracco C Aloj L Tarallo L Pedone C Morelli G 《ChemMedChem》2006,1(9):997-1006
A library of 14 cyclic peptide analogues derived from the octapeptide C-terminal sequence of the human cholecystokinin hormone (CCK(26-33), or CCK8) was designed, synthesized, and characterized. The 14 peptide analogues were rationally designed to specifically interact with the CCK type B receptor (CCK(B)-R) on the basis of the structure of the bimolecular complex between CCK8 and the third extracellular loop of CCK(B)-R, namely CCK(B)-R(352-379). The rational design of new ligands for CCK(B)-R has relied on stabilization by cyclic constraints of the structural motifs that bring the key residues of the ligand (especially Trp 30, Met 31, and Phe 33) in the proper spatial orientation for optimal interaction with the receptor. The binding affinity of the new ligands for CCK(B)-R was assessed by displacement experiments of (111)In-radiolabeled CCK8 in cells that overexpress the CCK(B) receptor. The new ligands generally showed binding affinities lower than that of parent CCK8, with the best compounds having IC50 values around 10 microM. Structure-activity relationship data show that preservation of the Trp 30-Met 31 motif is essential and that the Phe 33 side chain must be present. NMR conformational studies of the compound with maximal binding affinity (cyclo-B11, IC50=11 microM) in DPC micelles shows that this compound presents a turn-like conformation centered at the Trp 30-Met 31 segment, as planned by rational design. Such a conformation is stabilized by its interaction with the micelle rather than by the cyclic constraint. 相似文献
86.
Maria Cefola Maria L Amodio Rosaria Cornacchia Raffaella Rinaldi Sebastiano Vanadia Giancarlo Colelli 《Journal of the science of food and agriculture》2010,90(5):789-797
BACKGROUND: Many leafy brassicas are widely used for ready‐to‐use salads. Broccoli raab (Brassica rapa L.), also called turnip top, or rapini, is extensively cultivated in southern Italy. The edible portion is made up of the green, immature inflorescences and the stem with its most tender leaves. Recently, interest in this crop has increased among European consumers; moreover, a substantial increase in consumption could come from the ready‐to‐use product. RESULTS: The effects of four different atmosphere compositions (air, 3% O2 in nitrogen, 3% O2 + 10% CO2 in air, and 10% CO2 in air) on quality attributes of ready‐to‐use broccoli raab were studied. Controlled atmosphere affected appearance, composition, respiration rate, weight loss, and presence of off‐odours. Storage of broccoli raab florets under low oxygen conditions delayed post‐cutting deterioration during storage at 5 °C and preserved appearance and typical odour, up to 17 days. Moreover, respiration rate as well as loss of green colour, chlorophyll and vitamin C were also slowed down in this condition. Finally, in this study no effect of controlled atmosphere storage was found on total phenols content and antioxidant activity. CONCLUSION: Results showed that cold storage in 3% O2 can be beneficial in order to maintain quality of ready‐to‐use, broccoli raab for up to 17 days. Copyright © 2010 Society of Chemical Industry 相似文献
87.
Vito M. Paradiso Tommaso Gomes Raffaella Nasti Francesco Caponio Carmine Summo 《Food research international (Ottawa, Ont.)》2010,43(5):1389-1394
Several studies have investigated the interaction of free fatty acids with the oxidative phenomena involving oils during processing and storage. Nevertheless, the available information is insufficient and, in some cases, contradictory.The aim of this work was to throw light upon this matter, by evaluating – by means of different analytical approaches – the effect of adding increasing amounts of free fatty acids (0.25%, 0.5%, 1%, 3%) on the oxidative processes occurring in purified olive oil during oxidation at 60 °C.The results obtained showed that oxidized forms of triglycerides and polar oligopolymers of triglycerides increased during oxidation. Low amounts of added FFA caused a further increase of the levels of oxidized triglycerides and triglyceride oligopolymers – pointing out a pro-oxidant activity – while higher doses of added free fatty acids lead to lower amounts of oxidized forms of triglycerides respect to the purified oil. This could be due to an increase in peroxide decomposition exerted by free fatty acids when present in higher amounts. 相似文献
88.
89.
Raffaella?Saggin John?N.?CouplandEmail author 《Journal of the American Oil Chemists' Society》2004,81(1):27-32
Dispersions of coating fat in corn oil (2.5–12.5 wt%) were prepared following two different protocols: Type A dispersions
had an average crystal size of 30–36 μm, whereas type B dispersions were less than 1 μm. In both dispersions the fat crystals
were aggregated into larger structures (up to 80 μm). The longitudinal ultrasonic properties (i.e., velocity, attenuation,
and reflectance) were linearly related to the solid fat content, but only attenuation was sensitive to the different microstructures.
The velocity and reflectance measurements were modeled using the Urick equation. Shear ultrasonic reflectance and oscillatory
viscometry were used to measure the dynamic viscosity of all dispersions. According to both methods, type B samples were always
more viscous than type A at a similar solids content. The correlation between the two techniques was good (r
2>0.99), but the numeric agreement was different for both systems. 相似文献
90.