- Solid phase synthesis and SAR of small molecule agonists for the GPR40 receptor
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The discovery, synthesis and structure-activity relationship (SAR) of novel carboxylic acid agonists for GPR40 are described. Aryl propionic acid 1, identified from a high throughput screen, was selected for chemical exploration. Compound 2 was identified as our lead molecule through efficient solid phase combinatorial array chemistry and had an attractive in vitro and in vivo pharmacokinetic profile in rat. These ligands may prove useful in establishing a role for GPR40 in insulin regulation.
- McKeown, Stephen C.,Corbett, David F.,Goetz, Aaron S.,Littleton, Thomas R.,Bigham, Eric,Briscoe, Celia P.,Peat, Andrew J.,Watson, Steve P,Hickey, Deirdre M.B.
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- Bidirectional, iterative approach to the structural delineation of the functional "chemoprint" in GPR40 for agonist recognition
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GPR40, free fatty acid receptor 1 (FFAR1), is a member of the GPCR superfamily and a possible target for the treatment of type 2 diabetes. In this work, we conducted a bidirectional iterative investigation, including computational modeling and site-direct
- Tikhonova, Irina G.,Chi, Shing Sum,Neumann, Susanne,Thomas, Craig J.,Raaka, Bruce M.,Costanzi, Stefano,Gershengorn, Marvin C.
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- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER
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New uses for phenylketone carboxylate compounds and substituted aromatic compounds of Formula I, Formula I.1, Formula I.2, Formula IA, Formula IB, Formula IC and Formula II and their pharmaceutical acceptable salts for the treatment of cancer. The use of
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Page/Page column 41-42
(2012/08/07)
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- Synthesis and activity of small molecule GPR40 agonists
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The first report on the identification and structure-activity relationships of a novel series of GPR40 agonists based on a 3-(4-{[N-alkyl]amino}phenyl) propanoic acid template is described. Structural modifications to the original screening hit yielded co
- Garrido, Dulce M.,Corbett, David F.,Dwornik, Kate A.,Goetz, Aaron S.,Littleton, Thomas R.,McKeown, Steve C.,Mills, Wendy Y.,Smalley Jr., Terrence L.,Briscoe, Celia P.,Peat, Andrew J.
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p. 1840 - 1845
(2007/10/03)
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