title: Synthesis and biological evaluation of novel indoloazepine derivatives as non-peptide vasopressin V2 receptor antagonists.
abstract: A series of novel 3,4,5,6-tetrahydro-1H-azepino[4,3,2-cd]indoles was synthesized and tested for vasopressin receptor antagonist activity. We identified compounds with high affinity for the human V2 receptor and good selectivity over the human V1a receptor. Compound 6c bound to V2 receptors with an IC(50) value of 20 nM, had >100-fold selectivity over V1a receptors, and inhibited cAMP formation in a cellular V2 functional assay with an IC(50) value of 70 nM.
authors.affiliation: Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, Spring House, PA 19477-0776, USA. jmatthew@prius.jnj.com
authors.forename: Jay M
authors.initials: JM
authors.lastname: Matthews
authors.forename: Michael N
authors.initials: MN
authors.lastname: Greco
authors.forename: Leonard R
authors.initials: LR
authors.lastname: Hecker
authors.forename: William J
authors.initials: WJ
authors.lastname: Hoekstra
authors.forename: Patricia
authors.initials: P
authors.lastname: Andrade-Gordon
authors.forename: Lawrence
authors.initials: L
authors.lastname: de Garavilla
authors.forename: Keith T
authors.initials: KT
authors.lastname: Demarest
authors.forename: Eric
authors.initials: E
authors.lastname: Ericson
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Gunnet
authors.forename: William
authors.initials: W
authors.lastname: Hageman
authors.forename: Richard
authors.initials: R
authors.lastname: Look
authors.forename: John B
authors.initials: JB
authors.lastname: Moore
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Maryanoff
mesh_terms: D065092:Antidiuretic Hormone Receptor Antagonists; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D020128:Inhibitory Concentration 50; D011869:Radioligand Assay; D017483:Receptors, Vasopressin / Q000235:genetics; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001381:Azepines; D017483:Receptors, Vasopressin; D000242:Cyclic AMP