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1. chinaXiv:201711.02419 [pdf]

Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization

Xie, H(Xie, Hui); Zeng, LL(Zeng, Lili); Zeng, SG(Zeng, Shaogao); Lu, X (Lu, Xin); Zhang, GC (Zhang, Guicheng); Zhao, X (Zhao, Xin); Cheng, N (Cheng, Na); Tu, ZC (Tu, Zhengchao); Li, ZY (Li, Zhiyuan); Xu, HJ (Xu, Hongjiang); Yang, L (Yang, Ling); Zhang, XQ (Zhang, Xiquan); Huang, M (Huang, Min); Zhao, JL (Zhao, Junling); Hu, WH (Hu, Wenhui)
Subjects: Biology >> Ecology

We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development. (C) 2012 Elsevier Masson SAS. All rights reserved.

submitted time 2017-11-17 Hits471Downloads267 Comment 0

2. chinaXiv:201711.02424 [pdf]

Discovery of potent dipeptidyl peptidase IV inhibitors through pharmacophore hybridization and hit-to-lead optimization

Zeng, SG (Zeng, Shaogao); Xie, H (Xie, Hui); Zeng, LL (Zeng, Li-li); Lu, X (Lu, Xin); Zhao, X (Zhao, Xin); Zhang, GC (Zhang, Gui-cheng); Tu, ZC (Tu, Zheng-chao); Xu, HJ (Xu, Hong-jiang); Yang, L (Yang, Ling); Zhang, XQ (Zhang, Xi-quan); Hu, WH (Hu, Wenhui)
Subjects: Biology >> Ecology

A novel dipeptidyl peptidase IV inhibitor hit (5, IC50 = 0.86 mu M) was structurally derived from our recently disclosed preclinical candidate 4 by replacing the cyanobenzyl with a butynyl based on pharmacophore hybridization. A hit-to-lead optimization effort was then initiated to improve its potency. Most N-substituted analogs exhibited good in vitro activity, and compound 180 (IC50 = 1.55 nM) was identified to be a potent dipeptidyl peptidase IV inhibitor with a significantly improved pharmacokinetic properties (bioavailablity: 41% vs 82.9%; T-1/2: 2 h vs 4.9 h). (C) 2013 Elsevier Ltd. All rights reserved.

submitted time 2017-11-17 Hits464Downloads269 Comment 0

3. chinaXiv:201706.00767 [pdf]

Research on Online Safety Precaution Technology of a High-medium Pressure Gas Regulator

Hao Xuejun; Liu Xuha; Zhao Xin
Subjects: Dynamic and Electric Engineering >> Engineering Thermophysics

In view of some of the characteristics of a high-medium pressure gas regulator, such as small fault samples, many fault types and complex fault features etc, in order to improve the accuracy of fault precaution in this paper, a fault diagnosis method based on the combination of the improved wavelet packet and pressure harmonic distortion rate is proposed. On the basis of the harmonic distortion rate of the outlet pressure and the energy value of each frequency band obtained by improved wavelet packet decomposition, the rules for fault data were summarized. Finally, a safety precaution model of the high-medium pressure gas regulator is established.

submitted time 2017-06-26 From cooperative journals:《热科学学报》 Hits2014Downloads211 Comment 0

4. chinaXiv:201703.00287 [pdf]

Passive submillimeter-wave imaging demonstrated by a two-element interferometer

Han, Dong-Hao; Liu, Hao; Zhang, De-Hai; Meng, Jin; Zhao, Xin; Zhang, Ying; Wu, Ji
Subjects: Geosciences >> Space Physics

In this paper, an SMMW interferometric radiometer concept is demonstrated by a two-element interferometer with dedicated high accuracy SMMW devices. Point-source calibration method is introduced in order to reduce instrument errors. Interference fringes and point target images are presented by this SMMW interferometer. The linear phase error of the interference fringes is less than 2�and the angular resolution is better than 0.57� The measured performance characteristics of the two-element interferometer are consistent with the theoretical analysis. This interferometer demonstrates a new method for passive SMMW remote sensing. �2016, Science Press. All right reserved.

submitted time 2017-03-10 Hits983Downloads562 Comment 0

5. chinaXiv:201605.00280 [pdf]

MICAP (MICROWAVE IMAGER COMBINED ACTIVE AND PASSIVE): A NEW INSTRUMENT FOR CHINESE OCEAN SALINITY SATELLITE

Liu, Hao; Zhu, Di; Niu, Lijie; Wu, Lin; Wang, Caiyun; Chen, Xue; Zhao, Xin; Zhang, Cheng; Zhang, Xiangkun; Yin, Xiaobin; Wu, Ji
Subjects: Geosciences >> Space Physics

Sea surface salinity (SSS) plays an important role in global water cycle. In recent years, satellite based remote sensing has proven to be a promising approach for global SSS observation. A new payload concept, named MICAP (microwave imager combined active and passive), has been introduced in this paper. MICAP is a suit of active/passive instrument package, which includes L/C/K band one-dimensional MIR (microwave interferometric radiometer) and L-band DBF (digital beamforming) scatterometer, sharing a parabolic cylinder reflector. MICAP has been selected to be a candidate payload for future Chinese ocean salinity mission. In this paper, the MICAP instrument concept, specification and preliminary system design will be introduced.

submitted time 2016-05-03 Hits595Downloads409 Comment 0

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