Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists.
The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH-2), also found on eosinophils and basophils, is a prostaglandin D2 receptor involved in the recruitment of these cell types during an inflammatory response. In this report, we describe the synthesis and optimization of a ramatroban isostere that is a selective and potent antagonist of CRTH-2 which may be useful in the treatment of certain diseases.
Robarge
Michael J
MJ
Athersys, Inc., Medicinal Chemistry, 3201 Carnegie Avenue, Cleveland, OH 44115-2634, USA. mrobarge@athersys.com
Bom
David C
DC
Tumey
L Nathan
LN
Varga
Norbert
N
Gleason
Elizabeth
E
Silver
Daniel
D
Song
Jianping
J
Murphy
Steven M
SM
Ekema
George
G
Doucette
Chris
C
Hanniford
Doug
D
Palmer
Marc
M
Pawlowski
Gary
G
Danzig
Joel
J
Loftus
Margaret
M
Hunady
Karen
K
Sherf
Bruce A
BA
Mays
Robert W
RW
Stricker-Krongrad
Alain
A
Brunden
Kurt R
KR
Harrington
John J
JJ
Bennani
Youssef L
YL
D018927:Anti-Asthmatic Agents / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000737:chemistry* / Q000494:pharmacology*; D007536:Isomerism; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
D018927:Anti-Asthmatic Agents; D002227:Carbazoles; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; C063119:ramatroban; C036293:prostaglandin D2 receptor