title: 1,4-Diazepane compounds as potent and selective CB2 agonists: optimization of metabolic stability.
abstract: A high-throughput screening campaign has identified 1,4-diazepane compounds which are potent Cannabinoid receptor 2 agonists with excellent selectivity against the Cannabinoid receptor 1. This class of compounds suffered from low metabolic stability. Following various strategies, compounds with a good stability in liver microsomes and rat PK profile have been identified.
authors.affiliation: Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc, 900 Ridgebury Road, Ridgefield, CT 06877, USA. doris.riether@boehringer-ingelheim.com
authors.forename: Doris
authors.initials: D
authors.lastname: Riether
authors.forename: Lifen
authors.initials: L
authors.lastname: Wu
authors.forename: Pier F
authors.initials: PF
authors.lastname: Cirillo
authors.forename: Angela
authors.initials: A
authors.lastname: Berry
authors.forename: Edward R
authors.initials: ER
authors.lastname: Walker
authors.forename: Monika
authors.initials: M
authors.lastname: Ermann
authors.forename: Beatriz
authors.initials: B
authors.lastname: Noya-Marino
authors.forename: James E
authors.initials: JE
authors.lastname: Jenkins
authors.forename: Dan
authors.initials: D
authors.lastname: Albaugh
authors.forename: Claudia
authors.initials: C
authors.lastname: Albrecht
authors.forename: Michael
authors.initials: M
authors.lastname: Fisher
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Gemkow
authors.forename: Heather
authors.initials: H
authors.lastname: Grbic
authors.forename: Sabine
authors.initials: S
authors.lastname: Löbbe
authors.forename: Clemens
authors.initials: C
authors.lastname: Möller
authors.forename: Kathy
authors.initials: K
authors.lastname: O'Shea
authors.forename: Achim
authors.initials: A
authors.lastname: Sauer
authors.forename: Daw-Tsun
authors.initials: DT
authors.lastname: Shih
authors.forename: David S
authors.initials: DS
authors.lastname: Thomson
mesh_terms: D000818:Animals; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*
chemical_list: C545228:1,4-diazepane; D001381:Azepines; D043885:Receptor, Cannabinoid, CB2