Abstract
The discovery of highly potent and selective second generation EP(4) antagonist MK-2894 (34d) is discussed. This compound exhibits favorable pharmacokinetic profile in a number of preclinical species and potent anti-inflammatory activity in several animal models of pain/inflammation. It also shows favorable GI tolerability profile in rats when compared to traditional NSAID indomethacin.
MeSH terms
-
Analgesics / chemical synthesis*
-
Analgesics / chemistry
-
Analgesics / pharmacokinetics
-
Animals
-
Benzoates / chemical synthesis*
-
Benzoates / chemistry
-
Benzoates / pharmacokinetics
-
Cyclopropanes / chemical synthesis*
-
Cyclopropanes / chemistry
-
Cyclopropanes / pharmacokinetics
-
Half-Life
-
Humans
-
Magnetic Resonance Spectroscopy
-
Male
-
Pain / drug therapy
-
Prostaglandin Antagonists / chemical synthesis*
-
Prostaglandin Antagonists / chemistry
-
Prostaglandin Antagonists / pharmacokinetics
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, Prostaglandin E / antagonists & inhibitors
-
Receptors, Prostaglandin E / metabolism*
-
Structure-Activity Relationship
-
Thiophenes / chemical synthesis*
-
Thiophenes / chemistry
-
Thiophenes / pharmacokinetics
Substances
-
Analgesics
-
Benzoates
-
Cyclopropanes
-
Prostaglandin Antagonists
-
Receptors, Prostaglandin E
-
Thiophenes