title: Optimization of drug-like properties of nonsteroidal glucocorticoid mimetics and identification of a clinical candidate.
abstract: A series of nonsteroidal "dissociated" glucocorticoid receptor agonists was optimized for drug-like properties such as cytochrome P450 inhibition, metabolic stability, aqueous solubility, and hERG ion channel inhibition. This effort culminated in the identification of the clinical candidate compound ( R )-39.
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Christian
authors.initials: C
authors.lastname: Harcken
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Doris
authors.initials: D
authors.lastname: Riether
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Pingrong
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Hossein
authors.initials: H
authors.lastname: Razavi
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Usha
authors.initials: U
authors.lastname: Patel
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lee
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Todd
authors.initials: T
authors.lastname: Bosanac
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Yancey
authors.initials: Y
authors.lastname: Ward
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Ralph
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Donald
authors.initials: D
authors.lastname: Souza
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Nelson
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Alison
authors.initials: A
authors.lastname: Kukulka
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Tazmeen N
authors.initials: TN
authors.lastname: Fadra-Khan
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Zuvela-Jelaska
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Mita
authors.initials: M
authors.lastname: Patel
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: David S
authors.initials: DS
authors.lastname: Thomson
authors.affiliation: Department of Medicinal Chemistry and Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Nabozny
keywords: Glucocorticoid mimetics; anti-inflammatory agents; azaindoles; drug-like properties; glucocorticoid-induced osteoporosis; nonsteroidal glucocorticoids