title: Discovery of MK-7246, a selective CRTH2 antagonist for the treatment of respiratory diseases.
abstract: In this manuscript we wish to report the discovery of MK-7246 (4), a potent and selective CRTH2 (DP2) antagonist. SAR studies leading to MK-7246 along with two synthetic sequences enabling the preparation of this novel class of CRTH2 antagonist are reported. Finally, the pharmacokinetic and metabolic profile of MK-7246 is disclosed.
authors.affiliation: Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Kirkland, Québec, Canada. michel_gallant@videotron.ca
authors.forename: Michel
authors.initials: M
authors.lastname: Gallant
authors.forename: Christian
authors.initials: C
authors.lastname: Beaulieu
authors.forename: Carl
authors.initials: C
authors.lastname: Berthelette
authors.forename: John
authors.initials: J
authors.lastname: Colucci
authors.forename: Michael A
authors.initials: MA
authors.lastname: Crackower
authors.forename: Chad
authors.initials: C
authors.lastname: Dalton
authors.forename: Danielle
authors.initials: D
authors.lastname: Denis
authors.forename: Yves
authors.initials: Y
authors.lastname: Ducharme
authors.forename: Richard W
authors.initials: RW
authors.lastname: Friesen
authors.forename: Daniel
authors.initials: D
authors.lastname: Guay
authors.forename: François G
authors.initials: FG
authors.lastname: Gervais
authors.forename: Martine
authors.initials: M
authors.lastname: Hamel
authors.forename: Robert
authors.initials: R
authors.lastname: Houle
authors.forename: Connie M
authors.initials: CM
authors.lastname: Krawczyk
authors.forename: Birgit
authors.initials: B
authors.lastname: Kosjek
authors.forename: Stephen
authors.initials: S
authors.lastname: Lau
authors.forename: Yves
authors.initials: Y
authors.lastname: Leblanc
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Lee
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Levesque
authors.forename: Christophe
authors.initials: C
authors.lastname: Mellon
authors.forename: Carmela
authors.initials: C
authors.lastname: Molinaro
authors.forename: Wayne
authors.initials: W
authors.lastname: Mullet
authors.forename: Gary P
authors.initials: GP
authors.lastname: O'Neill
authors.forename: Paul
authors.initials: P
authors.lastname: O'Shea
authors.forename: Nicole
authors.initials: N
authors.lastname: Sawyer
authors.forename: Susan
authors.initials: S
authors.lastname: Sillaots
authors.forename: Daniel
authors.initials: D
authors.lastname: Simard
authors.forename: Deborah
authors.initials: D
authors.lastname: Slipetz
authors.forename: Rino
authors.initials: R
authors.lastname: Stocco
authors.forename: Dan
authors.initials: D
authors.lastname: Sørensen
authors.forename: Vouy Linh
authors.initials: VL
authors.lastname: Truong
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wong
authors.forename: Jin
authors.initials: J
authors.lastname: Wu
authors.forename: Helmi
authors.initials: H
authors.lastname: Zaghdane
authors.forename: Zhaoyin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D002243:Carbolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy*; D008253:Macaca mulatta; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C554899:((7R)-7-(((4-fluorophenyl)sulfonyl)(methyl)amino)-6,7,8,9-tetrahydropyrido(1,2-a)indol-10-yl)acetic acid; D002243:Carbolines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor