- Discovery and Characterization of Biased Allosteric Agonists of the Chemokine Receptor CXCR3
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In this work we report a design, synthesis, and detailed functional characterization of unique strongly biased allosteric agonists of CXCR3 that contain tetrahydroisoquinoline carboxamide cores. Compound 11 (FAUC1036) is the first strongly biased allosteric agonist of CXCR3 that selectively induces weak chemotaxis and leads to receptor internalization and the β-arrestin 2 recruitment with potency comparable to that of the chemokine CXCL11 without any activation of G proteins. A subtle structural change (addition of a methoxy group, 14 (FAUC1104)) led to a contrasting biased allosteric partial agonist that activated solely G proteins, induced chemotaxis, but failed to induce receptor internalization or β-arrestin 2 recruitment. Concomitant structure-activity relationship studies indicated very steep structure-activity relationships, which steer the ligand bias between the β-arrestin 2 and G protein pathway. Overall, the information presented provides a powerful platform for further development and rational design of strongly biased allosteric agonists of CXCR3.
- Milanos, Lampros,Brox, Regine,Frank, Theresa,Poklukar, Ga?per,Palmisano, Ralf,Waibel, Reiner,Einsiedel, Jürgen,Dürr, Maximilian,Ivanovi?-Burmazovi?, Ivana,Larsen, Olav,Hjort?, Gertrud Malene,Rosenkilde, Mette Marie,Tschammer, Nuska
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- Acylative Kinetic Resolution of Cyclic Hydroxamic Acids
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Racemic cyclic hydroxamic acids bearing an aryl substituent adjacent to the hydroxyl group undergo effective acylative kinetic resolution promoted by benzotetramisole (BTM).
- Yin, Jingwei,Straub, Matthew R.,Liao, Julian D.,Birman, Vladimir B.
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supporting information
p. 1546 - 1549
(2022/03/01)
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- AGONISTS OF THE CHEMOKINE RECEPTOR CXCR3
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The present invention relates to agonists of the chemokine receptor CXCR3, methods of their synthesis and uses thereof.
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Page/Page column 19
(2017/05/02)
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- Enantioselective Ruthenium(II)/Xyl-SunPhos/Daipen-Catalyzed hydrogenation of γ-Ketoamides
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A0series of γ-hydroxy amides were synthesized with high ena~tioselectivities (up to 99%) usyng asymmetric hydrogenation of the corresponding γ-ketoamides in the presence of Ru-Xyl-SunPhos-Daipen catalyst providing key building blocks for a variety of natu
- Zhao, Mengmeng,Li, Wanfang,Li, Xiaoming,Ren, Kai,Tao, Xiaoming,Xie, Xiaomin,Ayad, Tahar,Ratovelomanana-Vidal, Virginie,Zhang, Zhaowuo
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p. 6164 - 6171
(2014/07/21)
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- Chemical and biological studies of nakiterpiosin and nakiterpiosinone
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Nakiterpiosin and nakiterpiosinone are two related C-nor-D-homosteroids isolated from the sponge Terpios hoshinota that show promise as anticancer agents. We have previously described the asymmetric synthesis and revision of the relative configuration of
- Gao, Shuanhu,Wang, Qiaoling,Huang, Lily Jun-Shen,Lum, Lawrence,Chen, Chuo
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supporting information; scheme or table
p. 371 - 383
(2010/03/25)
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- Compound having effect of promoting neuron differentiation
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A novel cystacycline derivative which has an excellent effect of promoting the differentiation of neurons and is useful as a remedy for central nervous system disorders, a remedy for peripheral nerve disorders, etc.
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- The Stereoselective Synthesis of 2-Alkyl γ-Keto Acid and Heterocyclic Ketomethylene Peptide Isostere Core Units Using Chiral Alkylation by 2-Triflyloxy Esters
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A simple and general protocol for the enentioselective preparation of γ-keto acids and heterocyclic γ-keto acids which have an alkyl group at C-2 is reported.The alkyl group is introduced by chiral alkylation using a scalemic 2-triflyoxy ester.The alkylation takes place with inversion of configuration and is compatible with a variety of alkyl groups.This methodology is thus wellsuited for the preparation of a wide variety of ketomethylene peptide isosteres.
- Hoffman, Robert V.,Kim, Hwa-Ok
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p. 5107 - 5113
(2007/10/02)
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- OMEGA-HETEROAROYL(PROPIONYL OR BUTYRYL)-L-PROLINES
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This disclosure describes novel substituted ω-heteroaroyl(propionyl or butyryl)-L-prolines and the esters and cationic salts thereof which are useful as hypotensive agents in mammals.
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