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-indu...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2000-07, Vol.10 (13), p.1467-1470
Main Authors: GERSPACHER, M, VON SPRECHER, A, MAH, R, ANDERSON, G. P, BERTRAND, C, SUBRAMANIAN, N, HAUSER, K, BALL, H. A
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Anti-Asthmatic Agents - chemistry
Anti-Asthmatic Agents - metabolism
Anti-Asthmatic Agents - pharmacology
Aza Compounds - pharmacology
Benzamides - pharmacology
Biological and medical sciences
Bronchoconstriction - drug effects
Drug Design
Guinea Pigs
Medical sciences
Molecular Structure
Neurokinin A - analogs & derivatives
Neurokinin A - pharmacology
Neurokinin-1 Receptor Antagonists
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptide Fragments - pharmacology
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Receptors, Neurokinin-2 - antagonists & inhibitors
Stereoisomerism
Substance P - pharmacology
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(00)00260-2