- Design, synthesis, and analysis of antagonists of GPR55: Piperidine-substituted 1,3,4-oxadiazol-2-ones
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A series of 1,3,4-oxadiazol-2-ones was synthesized and tested for activity as antagonists at GPR55 in cellular beta-arrestin redistribution assays. The synthesis was designed to be modular in nature so that a sufficient number of analogues could be rapidly accessed to explore initial structure–activity relationships. The design of analogues was guided by the docking of potential compounds into a model of the inactive form of GPR55. The results of the assays were used to learn more about the binding pocket of GPR55. With this oxadiazolone scaffold, it was determined that modification of the aryl group adjacent to the oxadiazolone ring was often detrimental and that the distal cyclopropane was beneficial for activity. These results will guide further exploration of this receptor.
- Meza-Avi?a, Maria Elena,Lingerfelt, Mary A.,Console-Bram, Linda M.,Gamage, Thomas F.,Sharir, Haleli,Gettys, Kristen E.,Hurst, Dow P.,Kotsikorou, Evangelia,Shore, Derek M.,Caron, Marc G.,Rao, Narasinga,Barak, Larry S.,Abood, Mary E.,Reggio, Patricia H.,Croatt, Mitchell P.
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supporting information
p. 1827 - 1830
(2016/12/22)
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- Systematic investigation of halogen bonding in protein-ligand interactions
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Halogen bonding triggers activity: Increasing binding affinity was observed for a series of covalent human Cathepsin L inhibitors by exchanging an aryl ring H atom with Cl, Br, and I, which undergo halogen bonding with the C=O group of Gly61 in the S3 pocket of the enzyme. Fluorine, in contrast, strongly avoids halogen bonding (see scheme). The strong distance and angle dependence of halogen bonding was confirmed for biological systems. Copyright
- Hardegger, Leo A.,Kuhn, Bernd,Spinnler, Beat,Anselm, Lilli,Ecabert, Robert,Stihle, Martine,Gsell, Bernard,Thoma, Ralf,Diez, Joachim,Benz, Joerg,Plancher, Jean-Marc,Hartmann, Guido,Banner, David W.,Haap, Wolfgang,Diederich, Francois
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supporting information; experimental part
p. 314 - 318
(2011/02/28)
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- Synthesis of β-, γ-, and δ-lactams via Pd(II)-catalyzed C-H activation reactions
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Pd(II)-catalyzed intramolecular amination of sp2 and sp3 C-H bonds are developed using a combination of CuCl2 and AgOAc as the oxidant. The reaction protocol tolerates the presence of a double bond in the substrates. This catalytic reaction provides practical access to a wide range of β-, γ-, and δ-lactams. Copyright
- Wasa, Masayuki,Yu, Jin-Quan
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supporting information; experimental part
p. 14058 - 14059
(2009/03/11)
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