Analysis of crucial structural requirements of 2-substituted pyrimido[4,5-b][1,5]oxazocines as NK(1) receptor antagonist by axially chiral derivatives.
This study aimed to identify the crucial structural features of 2-substituted 8-methylpyrimido[4,5-b][1,5]oxazocine derivatives. Axially chiral 8-methylpyrimido[4,5-b][1,5]oxazocines bearing a substituent at the C-2 position were synthesized and evaluated as NK(1) antagonists. The results revealed that (aR, 8S)-stereochemistry and the substituent at the C-2 position are important for NK(1) receptor recognition.
Seto
Shigeki
S
Discovery Research Laboratories, Kyorin Pharmaceutical Co Ltd, 2399-1, Nogi, Nogi-Machi, Shimotsuga-Gun, Tochigi, Japan. shigeki.seto@mb.kyorin-pharm.co.jp
Asano
Jun
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D010079:Oxazocines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D064729:Neurokinin-1 Receptor Antagonists; D010079:Oxazocines