Combined tachykinin receptor antagonist: synthesis and stereochemical structure-activity relationships of novel morpholine analogues.
We report herein the synthesis and stereochemical structure-activity relationships of novel morpholine analogues 12 and 13 with regards to NK1, NK2 and NK3 tachykinin receptor binding affinity. An essential requirement for more potent binding affinities was controlled by absolute configuration. (S,R)-12 and (S,R)-13 exhibited high binding affinities for NK1, NK2 and NK3 receptors.
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan. takahi@shina.sankyo.co.jp
T
T
Nishi
K
K
Ishibashi
T
T
Takemoto
K
K
Nakajima
T
T
Fukazawa
Y
Y
Iio
K
K
Itoh
O
O
Mukaiyama
T
T
Yamaguchi
D000818:Animals; D006168:Guinea Pigs; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D009025:Morpholines; D018039:Receptors, Tachykinin; C037574:morpholine