Combined NK1 and NK2 tachykinin receptor antagonists: synthesis and structure-activity relationships of novel oxazolidine analogues.
We report herein the synthesis and structure-activity relationships of a series of novel oxazolidine analogues with regards to NK1 and NK2 tachykinin receptor binding affinity. Among this series of oxazolidine analogues, some compounds exhibited excellent high binding affinities for both NK1 and NK2 receptors. In addition, we describe the inhibitory effect in vivo on SP-induced airway vascular hyperpermeability and NKA-induced bronchoconstriction in guinea pigs.
Nishi
T
T
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Fukazawa
T
T
Ishibashi
K
K
Nakajima
K
K
Sugioka
Y
Y
Iio
Y
Y
Kurata
H
H
Itoh
K
K
Mukaiyama
O
O
Satoh
Y
Y
Yamaguchi
T
T
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008956:Models, Chemical; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D010080:Oxazoles; D018039:Receptors, Tachykinin; C064210:oxazolidine