Functionally selective M1 muscarinic agonists. 3. Side chain and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles
摘要:
In an attempt to improve upon the M(1) agonist activity of the selective M(1) agonist xanomeline and related compounds, the M(1) muscarinic efficacies and potencies of 3- and 6-substituted pyrazinylazacycles were varied by changing both the 3- and 6-substituents as well as the azacycle. Significant improvements in efficacy and potency over the previously prepared [3-(hexyloxy)pyrazinyl]tetrahydropyridine 19 were obtained with the [3-(hexyloxy)pyrazinyl]quinuclidine 5i. The M(1) activity of 5i showed some enantioselectivity with (S)-5i being ca. 4-fold more potent than (R)-5i. Like 19 and xanomeline, 5i was a functionally selective M(1) agonist that showed greater functional selectivity than widely studied pyrazinylquinuclidine 5n (L-689,660). The improved functional selectivity of 5i over 5n could be attributed to the additional binding interactions between the hexyloxy side chain of 5i and the M(1) receptor that are not available to 5n. Although 5i may show M(1) functional selectivity comparable to xanomeliine, 5i is a less efficacious and potent M(1) agonist than xanomeline.
1,2-Difunctionalization of Aryl Triflates: A Direct and Modular Access to Diversely Functionalized Anilines
作者:Seoyoung Cho、Qiu Wang
DOI:10.1021/acs.orglett.0c00320
日期:2020.2.21
ortho-Amino difunctionalization of aryl triflates has been achieved via a three-component reaction. The cascade reaction proceeds through a zincate base-mediated deprotonative formation of a reactive aryne intermediate, in situ nucleophilic addition, and coupling with electrophilic partners. This strategy leverages the advantageous reactivity of organozincate intermediates, enabling the installation
[EN] PHOSPHONATE CONJUGATES AND USES THEREOF<br/>[FR] CONJUGUÉS DE PHOSPHONATE ET LEURS UTILISATIONS
申请人:TRANSLATIONAL GENOMICS RES INST
公开号:WO2020150307A1
公开(公告)日:2020-07-23
Phosphonate conjugates, preferably, bisphosphonate conjugates; methods of inhibiting Ron receptor tyrosine kinase and methods of treatment of bone destruction due to cancer or other conditions utilizing the provided phosphonate conjugates.
Ethyl 2-hydroxy-2-methylpropanoate derivatives of magnesium and zinc. The effect of chelation on the homo- and copolymerization of lactide and ε-caprolactone
作者:Vagulejan Balasanthiran、Malcolm H. Chisholm、Kittisak Choojun、Christopher B. Durr
DOI:10.1039/c3dt52553h
日期:——
molecules have five coordinate Mg2+ ions that may be considered as derived from a trigonal bipyramid where the chelating BDI and OCMe2COOEt ligands span equatorial-axial sites. IR spectroscopic data obtained in CH2Cl2 indicate that the chelating nature of the OCMe2COOEt ligand is maintained in solution and variable temperature NMRstudies reveal that the ligands py or DMAP undergo a rapid reversible
Modified nucleotides, and methods to modify nucleotides with a moiety or label, such as biotin, that permits their detection and results in a modified nucleotide, and methods of use of the modified nucleotide in quantitative and qualitative assays.
Modified nucleotides, and methods to modify nucleotides with a moiety or label, such as biotin, that permits their detection and results in a modified nucleotide, and methods of use of the modified nucleotide in quantitative and qualitative assays.
The modified nucleotide compound having the structure (I): (P1)(P2)-Nucleoside(Nus)-Connecting Group (Alk)-Linking Group (Lnk)-Observable Label (Obs) (I).