- Discovery of GSK345931A: An EP1 receptor antagonist with efficacy in preclinical models of inflammatory pain
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Herein we describe the medicinal chemistry programme to identify a potential back-up compound to the EP1 receptor antagonist GW848687X. This work started with the lipophilic 1,2-biaryl benzene derivative 4 which displayed molecular weight of 41
- Hall, Adrian,Brown, Susan H.,Budd, Christopher,Clayton, Nicholas M.,Giblin, Gerard M.P.,Goldsmith, Paul,Hayhow, Thomas G.,Hurst, David N.,Naylor, Alan,Anthony Rawlings,Scoccitti, Tiziana,Wilson, Alexander W.,Winchester, Wendy J.
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scheme or table
p. 497 - 501
(2011/03/18)
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- New synthesis of 2-aryl-3-substituted benzo[b]furans from benzyl 2-halophenyl ethers
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Treatment of benzyl 2-halophenyl ethers with 3 equiv of t-BuLi results in Li-halogen exchange and lithiation at benzylic methylene simultaneously. These dianions do not undergo Wittig rearrangement and can be trapped with electrophiles. Their reactions with carboxylic esters afford the corresponding 2-aryl-3-hydroxy-2,3-dihydrobenzo[b]-furans as a mixture of diastereoisomers. Subsequent acid-catalyzed or mediated dehydration gives moderate to good overall yield of a variety of 2-aryl-3-substituted benzo[fe]-furans.
- Sanz, Roberto,Miguel, Delia,Martinez, Alberto,Perez, Antonio
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p. 4024 - 4027
(2007/10/03)
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- BIPHENYLOXYACETIC ACID DERIVATIVES FOR THE TREATMENT OF RESPIRATORY DISEASE
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The invention relates to substituted phenoxyacetic acids of formula (I), where the variables are as defined in claim 1, as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation.
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Page/Page column 31-32
(2008/06/13)
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- 2,3-Diarylthiophenes as selective EP1 receptor antagonists
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The synthesis and the EP1 receptor binding affinity of 2,3-diarylthiophene derivatives are described. The evaluation of the structure-activity relationship (SAR) in this series led to the identification of compounds 4, 7, and 12a, which exhibit high affinity for the human EP 1 receptor and a selectivity greater than 100-fold against the EP2, EP3, EP4, DP, FP, and IP receptors and greater than 25-fold versus the TP receptor. These three antagonists present good pharmacokinetics in rats and significant differences in the way they are distributed in the brain.
- Ducharme, Yves,Blouin, Marc,Carriere, Marie-Claude,Chateauneuf, Anne,Cote, Bernard,Denis, Danielle,Frenette, Richard,Greig, Gillian,Kargman, Stacia,Lamontagne, Sonia,Martins, Evelyn,Nantel, Francois,O'Neill, Gary,Sawyer, Nicole,Metters, Kathleen M.,Friesen, Richard W.
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p. 1155 - 1160
(2007/10/03)
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- NOVEL COMPOUNDS
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The invention relates to substituted phenoxyacetic acids (I) as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation
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- ASYMMETRIC SYNTHESIS OF HEXAHYDRODIBENZOFURANS BY STEREOSPECIFIC INVERSION OF ORTHO SUBSTITUTED 2-PHENYLCYCLOHEXANOLS
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This invention relates to the stereospecific process for the preparation, separation and purification of hexahydrodibenzofurans which are used in the preparation of the 5HT 3 compounds. More specifically, the present invention relates to a process for the
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