title: Novel lactam NK1 antagonists with anti-emetic activity.
abstract: A series of 4,4-disubstituted cyclohexylamine NK(1) antagonists containing a lactam ring is described. The compounds are brain penetrant and activity is demonstrated in a ferret emesis model.
authors.affiliation: Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. greg_hollingworth@merck.com
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hollingworth
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Carlson
authors.forename: José L
authors.initials: JL
authors.lastname: Castro
authors.forename: Gary G
authors.initials: GG
authors.lastname: Chicchi
authors.forename: Natalie
authors.initials: N
authors.lastname: Clark
authors.forename: Laura C
authors.initials: LC
authors.lastname: Cooper
authors.forename: Olivier
authors.initials: O
authors.lastname: Dirat
authors.forename: Jerry Di
authors.initials: JD
authors.lastname: Salvo
authors.forename: Jason M
authors.initials: JM
authors.lastname: Elliott
authors.forename: Ruth
authors.initials: R
authors.lastname: Kilburn
authors.forename: Marc M
authors.initials: MM
authors.lastname: Kurtz
authors.forename: Wayne
authors.initials: W
authors.lastname: Rycroft
authors.forename: F David
authors.initials: FD
authors.lastname: Tattersall
authors.forename: Kwei-Lan
authors.initials: KL
authors.lastname: Tsao
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Swain
mesh_terms: D000577:Amides / Q000737:chemistry; D000818:Animals; D000932:Antiemetics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005849:Gerbillinae; D006801:Humans; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008745:Methylation; D015394:Molecular Structure; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D015320:Tachykinins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D000932:Antiemetics; D007769:Lactams; D018040:Receptors, Neurokinin-1; D015320:Tachykinins