393509-23-4Relevant articles and documents
Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4- tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (MK-0524)
Sturino, Claudio F.,O'Neill, Gary,Lachance, Nicolas,Boyd, Michael,Berthelette, Carl,Labelle, Marc,Li, Lianhai,Roy, Bruno,Scheigetz, John,Tsou, Nancy,Aubin, Yves,Bateman, Kevin P.,Chauret, Nathalie,Day, Stephen H.,Lévesque, Jean-Fran?ois,Seto, Carmai,Silva, Jose H.,Trimble, Laird A.,Carriere, Marie-Claude,Denis, Danielle,Greig, Gillian,Kargman, Stacia,Lamontagne, Sonia,Mathieu, Marie-Claude,Sawyer, Nicole,Slipetz, Deborah,Abraham, William M.,Jones, Tom,McAuliffe, Malia,Piechuta, Hana,Nicoll-Griffith, Deborah A.,Wang, Zhaoyin,Zamboni, Robert,Young, Robert N.,Metters, Kathleen M.
, p. 794 - 806 (2007/10/03)
The discovery of the potent and selective prostaglandin D2 (PGD2) receptor (DP) antagonist [(3R)-4-(4-chlorobenzyl)-7-fluoro-5- (methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (13) is presented. Initial lead antagonists 6 and 7 were found to be potent and selective DP antagonists (DP Ki = 2.0 nM for each); however, they both suffered from poor pharmacokinetic profiles, short half-lives and high clearance rates in rats. Rat bile duct cannulation studies revealed that high concentrations of parent drug were present in the biliary fluid (Cmax = 1100 μM for 6 and 3900 μM for 7). This pharmacokinetic liability was circumvented by replacing the 7-methylsulfone substituent present in 6 and 7 with a fluorine atom resulting in antagonists with diminished propensity for biliary excretion and with superior pharmacokinetic profiles. Further optimization led to the discovery of the potent and selective DP antagonist 13.
METHOD OF TREATING ATHEROSCLEROSIS, DYSLIPIDEMIAS AND RELATED CONDITIONS
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Page/Page column 43, (2008/06/13)
A method of treating atherosclerosis is disclosed wherein nicotinic acid or another nicotinic acid receptor agonist is administered to the patient in combination with a DP receptor antagonist. The DP receptor antagonist is administered to reduce, prevent
NIACIN RECEPTOR AGONISTS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT
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Page/Page column 76, (2010/11/08)
The present invention encompasses compounds of Formula (I); as well as pharmaceutically acceptable salts and hydrates thereof, that are useful for treating dyslipidemias. Pharmaceutical compositions and methods of use are also included.