title: Identification of a new series of non-peptidic NK3 receptor antagonists.
abstract: The identification and structure-activity relationships of 2-aminomethyl-1-aryl cyclopropane carboxamides as novel NK(3) receptor antagonists are reported. The compound series was optimized to give analogues with low nanomolar binding to the NK(3) receptor and brain exposure, leading to activity in vivo in the senktide-induced hypoactivity model in gerbils.
authors.affiliation: Discovery Chemistry and DMPK, H. Lundbeck A/S, Valby, Denmark. kaju@lundbeck.com
authors.forename: Karsten
authors.initials: K
authors.lastname: Juhl
authors.forename: Tore
authors.initials: T
authors.lastname: Hansen
authors.forename: Jan
authors.initials: J
authors.lastname: Kehler
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Khanzhin
authors.forename: Morten B
authors.initials: MB
authors.lastname: Nørgaard
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruhland
authors.forename: Dorrit B
authors.initials: DB
authors.lastname: Larsen
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Jensen
authors.forename: Björn
authors.initials: B
authors.lastname: Steiniger-Brach
authors.forename: Søren M
authors.initials: SM
authors.lastname: Nielsen
authors.forename: Klaus B
authors.initials: KB
authors.lastname: Simonsen
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D005849:Gerbillinae; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D002264:Carboxylic Acids; D003521:Cyclopropanes; D010455:Peptides; D018042:Receptors, Neurokinin-3