95096-06-3Relevant articles and documents
8-Hydroxyquinolin-2(1H)-one analogues as potential β2-agonists: Design, synthesis and activity study
Xing, Gang,Zhi, Zhengxing,Yi, Ce,Zou, Jitian,Jing, Xuefeng,Yiu-Ho Woo, Anthony,Lin, Bin,Pan, Li,Zhang, Yuyang,Cheng, Maosheng
, (2021/07/19)
β2-Agonists that bind to plasmalemmal β2-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their β2-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC50 2-agonists among the compounds tested. They behaved as partial β2-agonists in non-overexpressed HEK293 cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary, B05 and C08 are β2-agonists with potential applicability in chronic respiratory diseases.
DATA PROCESSING DEVICE, PARTICULARLY A SET-TOP BOX FOR CONNECTION TO A RECEIVER, INPUT DEVICE FOR THE CONTROL OF A DATA PROCESSING DEVICE, AND METHOD FOR OPERATING A DATA PROCESSING DEVICE
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Page/Page column 25, (2008/06/13)
The invention relates to a data processing device, particularly a set-top box, and a method for operating the data processing device (16). The data processing device (16) is provided for the connection to a receiver (15) and a communication network. The data processing device (16) is configured to receive and process data sent from the communication network, comprising content data (2) and at least one identification date (3), and to transmit the processed data to the receiver (15) for the output thereof. The data processing device (16) is further configured to receive and process a code sent by an input device of the data processing device and/or of the receiver (15), the code being associated with a certain identification date (3) of the identification data. In response to the receipt of the code, a communication connection is established between the data processing device (16), or a communication terminal (19), and a unit of the communication network, which is associated with the certain identification date (3).
Structure-based design of inhibitors of purine nucleoside phosphorylase. 1. 9-(Arylmethyl) derivatives of 9-deazaguanine
Montgomery,Niwas,Rose,Secrist III,Babu,Bugg,Erion,Guida,Ealick
, p. 55 - 69 (2007/10/02)
Purine nucleoside phosphorylase (PNP, EC 2.4.2.1) is a salvage enzyme important to the T-cell-mediated part of the immune system and as such is an important therapeutic target. This paper describes the design, synthesis, and enzymatic evaluation of potent, competitive inhibitors of PNP. Potential inhibitors were designed using the three-dimensional structure of the enzyme in an iterative process that involved interactive computer graphics to model the native enzyme and complexes of it with the inhibitors, Monte Carlo-based conformational searching, and energy minimization. Studies of the enzyme/inhibitor complexes were used to determine priorities of the synthetic efforts. The resulting compounds were then evaluated by determination of their IC50 values and by X-ray diffraction analysis using difference Fourier maps. In this manner, we have developed a series of 9-(arylmethyl)- 9-deazapurines (2-amino-7-(arylmethyl)-4H-pyrrolo[3,2-d]-pyrimidin-4-ones) that are potent, membrane-permeable inhibitors of the enzyme. The IC50 values of these compounds range from 17 to 270 nM (in 1 mM phosphate), with 9-(3,4-dichlorobenzyl)-9-deazaguanine being the most potent inhibitor. X-ray analysis explained the role of the aryl groups and revealed the rearrangement of hydrogen bonds in the binding of the 9-deazaguanines in the active site of PNP relative to the binding of the 8-aminoguanines that results in more potent inhibition of the enzyme.
