比临床候选化合物 LY-2157299 选择性高 5.0 倍. 在 TGF-β 抑制剂的研究中发现这些罗丹宁化合物具有良好的抗真菌活 性, 而且对革兰氏阳性菌和革兰氏阴性菌显示很高的选择性. 它们显示与阳性对照化合物氟康唑(MIC＝1 µg/mL)类似 或更高的抗真菌活性(MIC＝0.5 or 1 µg/mL).

Many industrial processes and physical systems are spatially distributed systems. Recently, a novel 3-D FLC was developed for such systems. The previous study on the 3-D FLC was concentrated on an expert knowledge-based approach. However, in most of situations, we may lack the expert knowledge, while input-output data sets hidden with effective control laws are usually available. Under such circumstance, a data-driven approach could be a very effective way to design the 3-D FLC. In this study, we aim at developing a new 3-D FLC design methodology based on clustering and support vector machine (SVM) regression. The design consists of three parts: initial rule generation, rule-base simplification, and parameter learning. Firstly, the initial rules are extracted by a nearest neighborhood clustering algorithm with Frobenius norm as a distance. Secondly, the initial rule-base is simplified by merging similar 3-D fuzzy sets and similar 3-D fuzzy rules based on similarity measure technique. Thirdly, the consequent parameters are learned by a linear SVM regression algorithm. Additionally, the universal approximation capability of the proposed 3-D fuzzy system is discussed. Finally, the control of a catalytic packed-bed reactor is taken as an application to demonstrate the effectiveness of the proposed 3-D FLC design.

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Four series of novel pyrazole derivatives (compounds 17a-m, 18a-m, 19a-g, and 20a-g) were synthesized, and their antibacterial and antifungal activities were evaluated. Most of the target compounds (17a-m, 18k-m, and 19b-g) showed strong antifungal activity and high selectivity relative to both Gram-positive and Gramnegative bacteria. Among them, compounds 17l (minimum inhibitory concentration[MIC] = 0.25 µg/mL) and 17m (MIC = 0.25 µg/mL) showed the strongest antifungal activity, being 2-and 4-fold more active than the positive controls gatifloxacin and fluconazole, respectively. In particular, compound 17l showed little cytotoxicity against human LO2 cells and did not exhibit hemolysis at ultrahigh concentrations, as did the positive control compounds gatifloxacin and fluconazole. These results indicate that these compounds are valuable for further development as antifungal agents.