title: New indole amide derivatives as potent CRTH2 receptor antagonists.
abstract: A new series of indole amide acting as hCRTH2 receptor ligands had been explored and are described herein. Several amide derivatives displaying low nanomolar activity in hCRTH2 binding and whole blood assays were identified. They were found to behave as a full antagonists, exhibiting good selectivity over related prostaglandin receptors. Also, prototypical compounds in this novel series which displayed acceptable CYP profiles and were orally bioavailable in rats were identified.
authors.affiliation: Medicinal Chemistry, Merck Frosst, Center of Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Quebec, Canada H9H 3L1. Zaghdane.helmi@courrier.uqam.ca
authors.forename: Helmi
authors.initials: H
authors.lastname: Zaghdane
authors.forename: Michael
authors.initials: M
authors.lastname: Boyd
authors.forename: John
authors.initials: J
authors.lastname: Colucci
authors.forename: Daniel
authors.initials: D
authors.lastname: Simard
authors.forename: Carl
authors.initials: C
authors.lastname: Berthelette
authors.forename: Yves
authors.initials: Y
authors.lastname: Leblanc
authors.forename: Zhaoyin
authors.initials: Z
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Houle
authors.forename: Jean François
authors.initials: JF
authors.lastname: Lévesque
authors.forename: Carmela
authors.initials: C
authors.lastname: Molinaro
authors.forename: Martine
authors.initials: M
authors.lastname: Hamel
authors.forename: Rino
authors.initials: R
authors.lastname: Stocco
authors.forename: Nicole
authors.initials: N
authors.lastname: Sawyer
authors.forename: Susan
authors.initials: S
authors.lastname: Sillaots
authors.forename: François
authors.initials: F
authors.lastname: Gervais
authors.forename: Michel
authors.initials: M
authors.lastname: Gallant
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists*
chemical_list: D000577:Amides; D007211:Indoles; D008024:Ligands; D017448:Receptors, Dopamine D2