mk-0524 and Airway-Obstruction

mk-0524 has been researched along with Airway-Obstruction* in 1 studies

Other Studies

1 other study(ies) available for mk-0524 and Airway-Obstruction

Article	Year
Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (MK-0524). Journal of medicinal chemistry, 2007, Feb-22, Volume: 50, Issue:4 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 microM for 6 and 3900 microM 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. Topics: Airway Obstruction; Animals; Bile; Binding, Competitive; Dogs; Hepatocytes; Humans; In Vitro Techniques; Indoles; Macaca fascicularis; Male; Mice; Microsomes; Nasal Decongestants; Protein Binding; Rats; Rats, Sprague-Dawley; Receptors, Immunologic; Receptors, Prostaglandin; Sheep; Stereoisomerism; Structure-Activity Relationship	2007

Article

Year

Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (MK-0524).

Journal of medicinal chemistry, 2007, Feb-22, Volume: 50, Issue:4

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 microM for 6 and 3900 microM 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.

Topics: Airway Obstruction; Animals; Bile; Binding, Competitive; Dogs; Hepatocytes; Humans; In Vitro Techniques; Indoles; Macaca fascicularis; Male; Mice; Microsomes; Nasal Decongestants; Protein Binding; Rats; Rats, Sprague-Dawley; Receptors, Immunologic; Receptors, Prostaglandin; Sheep; Stereoisomerism; Structure-Activity Relationship

2007