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Haichao Zhu Meihua Liu Haiyan Li Ting Guan Qi Zhang Yang Chen Yingxiang Liu Rolf R. Hartmann Lina Yin Qingzhong Hu 《中国化学快报》2021,32(7):2327-2332
Exorbitant aldosterone is closely associated with various severe diseases, including congestive heart failure and chronic kidney disease. As aldosterone synthase is the pivotal enzyme in aldosterone biosynthesis, its inhibition constitutes a promising treatment for these diseases. Via a structure-based approach, a series of pyridyl substituted 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-ones were designed as inhibitors of aldosterone synthase. Six compounds (5j, 5l, 5m 5w, 5x and 5y) distinguished themselves with potent inhibition (IC50 <100 nmol/L) and high selectivity over homogenous 11β-hydroxylase. As the most promising compound, 5x exhibited an IC50 of 12 nmol/L and an excellent selectivity factor (SF) of 157, which are both superior to those of the reference fadrazole (IC50 = 21 nmol/L, SF = 7). Importantly, 5x showed no inhibition against steroidogenic CYP17, CYP19 and a panel of hepatic CYP enzymes indicating an outstanding safety profile. As it manifested satisfactory pharmacokinetic properties in rats, compound 5x was considered as a drug candidate for further development. 相似文献
904.
Dr. Ze-Jie Lv Wei Liu Miaomiao Zhu Zhengqi Chai Junnian Wei Prof. Wen-Xiong Zhang 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(66):16498-16504
Although the reaction chemistry of transition metallacyclopropenes has been well-established in the last decades, the reactivity of rare-earth metallacyclopropenes remains elusive. Herein, we report the reaction of lutetacyclopropene 1 toward a series of unsaturated molecules. The reaction of 1 with one equiv. of PhCOMe, Ar1CHO (Ar1=2,6-Me2C6H3), W(CO)6, and PhCH=NPh provided oxalutetacyclopentenes, metallacyclic lutetoxycarbene, and azalutetacyclopentene via 1,2-insertion of C=O, C≡O, or C=N bonds into Lu−Csp2 bond, respectively. However, the reaction between 1 and Ar2N=C=NAr2 (Ar2=4-MeC6H4) gave an acyclic lutetium complex with a diamidinate ligand by the coupling of one molecule of 1 with two carbodiimides, irrespective of the amount of carbodiimide employed. More interestingly, when 1 was treated with two equiv. of Ar1CHO, the reductive coupling of two C=O bonds was discovered to give a lutetium pinacolate complex along with the release of tolan. Remarkably, the reactivity of 1 is significantly different from that of scandacyclopropenes; these metallacycles derived from 1 all represent the first cases in rare-earth organometallic chemistry. 相似文献
905.
Ni Xie Qi-Zhi Zhu Jian-Fu Shao Li-Hua Xu 《International Journal of Solids and Structures》2012,49(6):919-928
In this paper, we propose a micromechanical analysis of damage and related inelastic deformation in saturated porous quasi brittle materials. The materials are weakened by randomly distributed microcracks and saturated by interstitial fluid with drained and undrained conditions. The emphasis is put on the closed cracks under compression-dominated stresses. The material damage is related to the frictional sliding on crack surface and described by a local scalar variable. The effective properties of the materials are determined using a linear homogenization approach, based on the extension of Eshelby’s inclusion solution to penny shaped cracks. The inelastic behavior induced by microcracks is described in the framework of the irreversible thermodynamics. As an original contribution, the potential energy of the saturated materials weakened by closed frictional microcracks is determined and formulated as a sum of an elastic part and a plastic part, the latter entirely induced by frictional sliding of microcracks. The influence of fluid pressure is accounted for in the friction criterion through the concept of local effective stress at microcracks. We show that the Biot’s effective stress controls the evolution of total strain while the local Terzaghi’s effective stress controls the evolution of plastic strain. Further, the frictional sliding between crack lips generates volumetric dilatancy and reduction in fluid pressure. Applications of the proposed model to typical brittle rocks are presented with comparisons between numerical results and experimental data in both drained and undrained triaxial tests. 相似文献
906.
We present a high power red-green-blue (RGB) laser light source based on cascaded quasi-phasematched wavelength conversions
in a single stoichiometric lithium tantalate. The superiority of the experimental setup is: the facula of the incident beam
is elliptical to increase interaction volume, and the cavity was an idler resonant configuration for realizing more efficient
red and blue light output. An average power of 2 W of quasi-white-light was obtained by proper combination of the RGB three
colors. The conversion efficiency for the power of the quasi-white-light over pump power reached 36%. This efficiency and
powerful RGB laser light source has potential applications in laser-based projection display et al. 相似文献
907.
Xie Puhui Zhu Yanru Huang Xuewei Gao Guangqin Guo Fengqi Yang Guoyu 《Research on Chemical Intermediates》2018,44(4):2823-2837
Research on Chemical Intermediates - A new near-infrared fluorescent “turn-on” chemodosimeter (probe 1) based on dicyanomethylene-4H-chromene fluorophore for sulfide was developed.... 相似文献
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