title: Aryl 1,4-diazepane compounds as potent and selective CB2 agonists: optimization of drug-like properties and target independent parameters.
abstract: A high throughput screening campaign identified aryl 1,4-diazepane compounds as potent and selective cannabinoid receptor 2 agonists as compared to cannabinoid receptor 1. This class of compounds suffered from poor drug-like parameters as well as low microsomal stability and poor solubility. Structure-activity relationships are described with a focus on improving the drug-like parameters resulting in compounds with improved solubility and permeability.
authors.affiliation: Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, USA. renee.zindell@boehringer-ingelheim.com
authors.forename: Renée
authors.initials: R
authors.lastname: Zindell
authors.forename: Edward R
authors.initials: ER
authors.lastname: Walker
authors.forename: John
authors.initials: J
authors.lastname: Scott
authors.forename: Patricia
authors.initials: P
authors.lastname: Amouzegh
authors.forename: Lifen
authors.initials: L
authors.lastname: Wu
authors.forename: Monika
authors.initials: M
authors.lastname: Ermann
authors.forename: David
authors.initials: D
authors.lastname: Thomson
authors.forename: Micheal B
authors.initials: MB
authors.lastname: Fisher
authors.forename: Cody Lee
authors.initials: CL
authors.lastname: Fullenwider
authors.forename: Heather
authors.initials: H
authors.lastname: Grbic
authors.forename: Paul
authors.initials: P
authors.lastname: Kaplita
authors.forename: Brian
authors.initials: B
authors.lastname: Linehan
authors.forename: Mita
authors.initials: M
authors.lastname: Patel
authors.forename: Monica
authors.initials: M
authors.lastname: Patel
authors.forename: Sabine
authors.initials: S
authors.lastname: Löbbe
authors.forename: Svenja
authors.initials: S
authors.lastname: Block
authors.forename: Claudia
authors.initials: C
authors.lastname: Albrecht
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Gemkow
authors.forename: Daw-Tsun
authors.initials: DT
authors.lastname: Shih
authors.forename: Doris
authors.initials: D
authors.lastname: Riether
mesh_terms: D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D057166:High-Throughput Screening Assays; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: C545228:1,4-diazepane; D001381:Azepines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2