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排序方式: 共有10000条查询结果,搜索用时 187 毫秒
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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
3.
Dr. Li Di Prof. Per Artursson Dr. Alex Avdeef Prof. Leslie Z. Benet Prof. J. Brian Houston Dr. Manfred Kansy Edward H. Kerns Prof. Hans Lennernäs Dr. Dennis A. Smith Prof. Kiyohiko Sugano 《ChemMedChem》2020,15(20):1862-1874
Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients. 相似文献
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Navab SinghAuthor Vitae Moitreyee Mukherjee-RoyAuthor VitaeSohan Singh MehtaAuthor Vitae 《Microelectronics Journal》2003,34(4):237-245
The patterning of contact holes by selecting out-of-focus image plane (defocus) using attenuated phase shift masks (APSM) has been studied. Defocus is found to enhance the image modulation at low partial coherence for contact holes with negative local average of mask function. Semi-dense holes up to 130 nm in 8% APSM have been printed by 0.5 μm defocus at a partial coherence of 0.31 using KrF scanner with highest numerical aperture of 0.68. However, these holes were closed with in-focus imaging. Defocus is also found to be beneficial for patterning the pitches that have extensive side lobes with in-focus imaging. 相似文献
6.
Diese Recherche zeigt, dass sich die Bedeutung, die dem Thema RFID in den Medien und der ?ffentlichen Diskussion derzeit beigemessen
wird, auch in der Anzahl der im Internet zu findenden Seiten niederschl?gt. Dabei bewegt sich die Qualit?t der betrachteten
Angebote überwiegend auf einem hohen Niveau, was vor allem auf Seiten der kommerziellen Anbieter nicht weiter verwundert,
da es sich bei RFID doch um einen zunehmend st?rker umk?mpften Markt handelt, auf dem es hei?t, potenzielle Kunden für sich
zu akquirieren. Es darf mit Spannung erwartet werden, wie sich das Informationsangebot wandelt, wenn tats?chlich das prognostizierte
exponentielle Wachstum des RFID-Marktes eintritt. 相似文献
7.
The curing of diglycidyl ether of bisphenol A (DGEBA) with 2,6-dimethylol-p-cresol modified by hexahydrophthalic acid anhydride was investigated and compared with the analogous in situ curing of DGEBA, hexahydrophthalic acid anhydride and 2,6-dimethylol-p-cresol. The chemical reactions were investigated by means of titration and different spectroscopic and chromatographic methods. It was examined whether the less complicated and therefore cheaper in situ reaction delivers postcured products with equal or better properties. Furthermore, it was investigated whether the results are similar using technical phenolic hardeners. 相似文献
8.
Adaptive motion control using neural network approximations 总被引:1,自引:0,他引:1
In this paper, we present a new adaptive technique for tracking control of mechanical systems in the presence of friction and periodic disturbances. Radial Basis Functions (RBFs) are used to compensate for the effects of nonlinearly occurring parameters in the friction and periodic disturbance model. Theoretical analysis, such as stability and transient performance, is provided. Furthermore, the performance of the adaptive RBF controller and its non-adaptive counterpart are compared. 相似文献
9.
Cherng-Min MaAuthor Vitae 《Pattern recognition》2003,36(8):1775-1782
Generally, a reduction operation (e.g., thinning and shrinking) on 3D binary images can be represented as a set of reduction templates where every object voxel of the image satisfying any template is turned to a background voxel. Generally, it is rather difficult, error-prone and time-consuming for verifying the topological soundness of a 3D parallel reduction operation. This paper proposes sufficient conditions of time complexity O(n) for verifying the topological soundness of 3D parallel 6-subiteration reduction operations of n templates where such a kind of 3D reduction operations is performed alternatively from the six orthogonal directions to turn object voxels to background voxels. By such sufficient conditions, the topology soundness of a 3D 6-subiteration parallel reduction operation can be verified by checking each and every of its templates. 相似文献
10.
In this paper, we present a control methodology for a class of discrete time nonlinear systems that depend on a possibly exogenous scheduling variable. This class of systems consists of an interpolation of nonlinear dynamic equations in strict feedback form, and it may represent systems with a time-varying nonlinear structure. Moreover, this class of systems is able to represent some cases of gain scheduling control, Takagi-Sugeno fuzzy systems, as well as input-output realizations of nonlinear systems which are approximated via localized linearizations. We present two control theorems, one using what we call a “global” approach (akin to traditional backstepping), and a “local” approach, our main result, where backstepping is again used but the control law is an interpolation of local control terms. An aircraft wing rock regulation problem with varying angle of attack is used to illustrate and compare the two approaches. 相似文献