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.
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.
Gerspacher
M
M
Pharma Research, Novartis Pharma AG, Basel, Switzerland. marc.gerspacher@pharma.novartis.com
von Sprecher
A
A
Mah
R
R
Anderson
G P
GP
Bertrand
C
C
Subramanian
N
N
Hauser
K
K
Ball
H A
HA
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
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