title: Identification of prostaglandin D2 receptor antagonists based on a tetrahydropyridoindole scaffold.
abstract: A new series of indole-based antagonists of the PGD(2) receptor subtype 1 (DP1 receptor) was identified and the progress of the structure-activity relationship study to the identification of potent and selective antagonists is presented. Selective DP1 antagonists with high potency and selectivity were prepared. Of particular interest is the DP1 antagonist 26 with a K(i) value of 1 nM for the DP1 receptor and an IC(50) value of 4.6 nM in a DP1 functional assay for the inhibition of the PGD(2) induced cAMP production in platelet rich plasma (PRP).
authors: Department of Medicinal Chemistry, Merck Frosst Canada & Co., 16711 Trans Canada Hwy, Kirkland, Que., Canada. christian_beaulieu@merck.com
authors: Christian
authors: C
authors: Beaulieu
authors: Daniel
authors: D
authors: Guay
authors: Zhaoyin
authors: Z
authors: Wang
authors: Yves
authors: Y
authors: Leblanc
authors: Patrick
authors: P
authors: Roy
authors: Claude
authors: C
authors: Dufresne
authors: Robert
authors: R
authors: Zamboni
authors: Carl
authors: C
authors: Berthelette
authors: Stephen
authors: S
authors: Day
authors: Nancy
authors: N
authors: Tsou
authors: Danielle
authors: D
authors: Denis
authors: Gillian
authors: G
authors: Greig
authors: Marie-Claude
authors: MC
authors: Mathieu
authors: Gary
authors: G
authors: O'Neill
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D011725:Pyridines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D006859:Hydrogen; C023666:pyridine; C036293:prostaglandin D2 receptor