398148-07-7Relevant articles and documents
Dual neurokinin NK1/NK2 antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5- bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N′- methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides
Gerspacher, Marc,La Vecchia, Luigi,Mah, Robert,Von Sprecher, Andreas,Anderson, Gary P.,Subramanian, Natarajan,Hauser, Kathleen,Bammerlin, Heinrich,Kimmel, Sabine,Pawelzik, Viviane,Ryffel, Karin,Ball, Howard A.
, p. 3081 - 3084 (2007/10/03)
Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N- methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK2 affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N- methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK2 receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N′- methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK1/NK2 antagonist.
