title: N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide: an orally active neurokinin NK1/NK2 antagonist.
abstract: The stereoselective synthesis of N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl+ ++)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide (4) and its NK1 and NK2 receptor binding properties are reported. In addition the potent inhibitory effects in vivo on sar9-SP- and beta-Ala-NKA-induced airway bronchoconstriction in guinea pigs are demonstrated.
authors.affiliation: Pharma Research, Novartis Pharma AG, Basel, Switzerland. marc.gerspacher@pharma.novartis.com
authors.forename: M
authors.initials: M
authors.lastname: Gerspacher
authors.forename: A
authors.initials: A
authors.lastname: von Sprecher
authors.forename: R
authors.initials: R
authors.lastname: Mah
authors.forename: G P
authors.initials: GP
authors.lastname: Anderson
authors.forename: C
authors.initials: C
authors.lastname: Bertrand
authors.forename: N
authors.initials: N
authors.lastname: Subramanian
authors.forename: K
authors.initials: K
authors.lastname: Hauser
authors.forename: H A
authors.initials: HA
authors.lastname: Ball
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001372:Aza Compounds / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects; D015195:Drug Design; D006168:Guinea Pigs; D015394:Molecular Structure; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013373:Substance P / Q000494:pharmacology
chemical_list: D018927:Anti-Asthmatic Agents; D001372:Aza Compounds; D001549:Benzamides; C415227:N-(1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl)-allyl)-N-methyl-3,5,-bis-trifluoromethyl-benzamide; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; C064218:neurokinin A (4-10), beta-Ala(8)-; D013373:Substance P; D015288:Neurokinin A