title: Identification of an indole series of prostaglandin D2 receptor antagonists.
abstract: A novel indole series of PGD2 receptor (DP receptor) antagonists is presented. Optimization of this series led to the identification of potent and selective DP receptor antagonists. In particular, antagonists 35 and 36 were identified with Ki values of 2.6 and 1.8 nM, respectively. These two antagonists are also potent in a DP functional assay where they inhibit the PGD2 induced cAMP production in platelet rich plasma with IC50 values of 7.9 and 8.6 nM, respectively. The structure-activity relationships of this indole series of DP receptor antagonists will also be discussed.
authors.affiliation: Department of Medicinal Chemistry, Merck Frosst Canada & Co., 16711 Trans Canada Hwy. Kirkland, Que., Canada H9H 3L1. claudio_sturino@merck.com
authors.forename: Claudio F
authors.initials: CF
authors.lastname: Sturino
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lachance
authors.forename: Michael
authors.initials: M
authors.lastname: Boyd
authors.forename: Carl
authors.initials: C
authors.lastname: Berthelette
authors.forename: Marc
authors.initials: M
authors.lastname: Labelle
authors.forename: Lianhai
authors.initials: L
authors.lastname: Li
authors.forename: Bruno
authors.initials: B
authors.lastname: Roy
authors.forename: John
authors.initials: J
authors.lastname: Scheigetz
authors.forename: Nancy
authors.initials: N
authors.lastname: Tsou
authors.forename: Christine
authors.initials: C
authors.lastname: Brideau
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cauchon
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Carriere
authors.forename: Danielle
authors.initials: D
authors.lastname: Denis
authors.forename: Gillian
authors.initials: G
authors.lastname: Greig
authors.forename: Stacia
authors.initials: S
authors.lastname: Kargman
authors.forename: Sonia
authors.initials: S
authors.lastname: Lamontagne
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Mathieu
authors.forename: Nicole
authors.initials: N
authors.lastname: Sawyer
authors.forename: Deborah
authors.initials: D
authors.lastname: Slipetz
authors.forename: Gary
authors.initials: G
authors.lastname: O'Neill
authors.forename: Zhaoyin
authors.initials: Z
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Zamboni
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Metters
authors.forename: Robert N
authors.initials: RN
authors.lastname: Young
mesh_terms: D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012451:Safrole / Q000031:analogs & derivatives / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C030374:indole; D012451:Safrole; C005746:sulfoxide; C036293:prostaglandin D2 receptor