title: Discovery of indole inhibitors of chemokine receptor 9 (CCR9).
abstract: Irritable bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) are serious chronic diseases affecting millions of patients worldwide. Studies of human chemokine biology has suggested C-C chemokine receptor 9 (CCR9) may be a key mediator of pro-inflammatory signaling. Discovery of agents that inhibit CCR9 may lead to new therapies for CD and UC patients. Herein we describe the evolution of a high content screening hit (1) into potent inhibitors of CCR9, such as azaindole 12.
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States. Electronic address: pandya.bhaumik@gmail.com.
authors.forename: Bhaumik A
authors.initials: BA
authors.lastname: Pandya
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Christian
authors.initials: C
authors.lastname: Baber
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Audrey
authors.initials: A
authors.lastname: Chan
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Chamberlain
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Haoqun
authors.initials: H
authors.lastname: Chandonnet
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Goss
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Timothy
authors.initials: T
authors.lastname: Hopper
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Blaise
authors.initials: B
authors.lastname: Lippa
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Katherine
authors.initials: K
authors.lastname: Poutsiaka
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Jan
authors.initials: J
authors.lastname: Romero
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Stucka
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Varoglu
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cubist Pharmaceuticals, Discovery Chemistry, 65 Hayden Avenue, Lexington, MA 021421, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D054388:Receptors, CCR / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C119309:CC chemokine receptor 9; D007211:Indoles; D054388:Receptors, CCR; C030374:indole
keywords: Crohn’s disease (CD); C–C chemokine receptor 9 (CCR9); Irritable bowel disease (IBD); Ulcerative colitis (UC)