Synthesis and activity of small molecule GPR40 agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 7, 2006, Pages 1840-1845

  Garrido, Dulce M ^a   Corbett, David F ^b   Dwornik, Kate A ^a   Goetz, Aaron S ^a   Littleton, Thomas R ^a   McKeown, Steve C ^b   Mills, Wendy Y ^a   Smalley Jr , Terrence L ^a   Briscoe, Celia P ^a   Peat, Andrew J ^a  

^a GLAXOSMITHKLINE   (United States)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Asymmetric cyclopropanation; Fatty acid receptor; G protein coupled receptor agonist; GPCR agonist; GPR40; GPR40 agonists; Type 2 diabetes

Indexed keywords

ANTIDIABETIC AGENT; CARBOXYLIC ACID; G PROTEIN COUPLED RECEPTOR 40 STIMULATING AGENT; HORMONE RECEPTOR STIMULATING AGENT; PROPIONIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

AGONIST; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; NON INSULIN DEPENDENT DIABETES MELLITUS; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ALKANES; ANIMALS; CHO CELLS; CRICETINAE; HUMANS; PROPIONIC ACIDS; RECEPTORS, G-PROTEIN-COUPLED; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33144463383     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.01.007     Document Type: Article

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7. 2 were added. The crude product was purified on silica gel (hexanes/ethyl acetate).
8. 4, filtered, and concentrated to give the pure carboxylic acid.
9. 3 solution and ethyl acetate were added. The crude products were purified on silica gel (hexanes/ethyl acetate).
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16. 3) δ 7.95 (br s, 1H), 7.46 (d, J = 8 Hz, 2H), 7.10 (d, J = 8 Hz, 2H), 4.16 (q, J = 7 Hz, 2H), 2.50 (m, 1H), 1,87 (m, 1H), 1.60 (m, 1H), 1.28 (m, 1H), 1.27 (t, J = 7 Hz, 3H).
17. A manuscript describing the in vitro biology of compound 2A has been submitted: Briscoe, C. B.; Peat, A. J.; McKeown, S. C.; Corbett, D. F.; Goetz, A. S.; Littleton, T. R.; McCoy, D. C.; Kenakin, T. P.; Andrews, J. L.; Ammala, C.; Fornwald, J. A.; Ignar, D. M., Jenkinson, S. Br. J. Pharmacol. Accepted.