Abstract
An extensive structure-activity study based around the high-affinity leukotriene B4 (LTB4) receptor antagonist SB 201146 (1) led to the identification of (E)-3-[6-[[(2,6-dichlorophenyl)-thio]methyl]-3-(2-phenylethoxy)-2- pyridinyl]-2-propenoic acid (3). This compound displays high affinity for the human neutrophil LTB4 receptor (Ki = 0.78 nM), blocks LTB4-induced Ca2+ mobilization with an IC50 of 6.6 +/- 1.5 nM, and demonstrates potent oral and topical antiinflammatory activity in a murine model of dermal inflammation.
MeSH terms
-
Acrylates / chemistry*
-
Acrylates / metabolism
-
Acrylates / pharmacology
-
Animals
-
Anti-Inflammatory Agents
-
Arachidonic Acid
-
Calcium / metabolism
-
Cytoplasmic Granules / drug effects
-
Cytoplasmic Granules / physiology
-
Humans
-
Leukotriene B4 / pharmacology
-
Mice
-
Mice, Inbred BALB C
-
Molecular Structure
-
Neutrophils / metabolism
-
Neutrophils / ultrastructure
-
Otitis / chemically induced
-
Otitis / drug therapy
-
Pyridines / chemistry*
-
Pyridines / metabolism
-
Pyridines / pharmacology
-
Receptors, Leukotriene B4 / antagonists & inhibitors*
-
Receptors, Leukotriene B4 / metabolism
-
Structure-Activity Relationship
Substances
-
Acrylates
-
Anti-Inflammatory Agents
-
Pyridines
-
Receptors, Leukotriene B4
-
SB 201146
-
Leukotriene B4
-
Arachidonic Acid
-
Ticolubant
-
Calcium