3,4-Dihydro-2H-benzo[1,4]oxazine derivatives as 5-HT6 receptor antagonists.
A series of novel 3,4-dihydro-2H-benzo[1,4]oxazine derivatives has been designed and synthesized as 5-HT(6) receptor antagonists. Many of the compounds displayed subnanomolar affinities for the 5-HT(6) receptor and good brain penetration in rats. The relationship of structure and lipophilicity to hERG inhibition of this series of compounds is discussed.
Zhao
Shu-Hai
SH
Roche Pharmaceuticals, Medicinal Chemistry, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. shu-hai.zhao@roche.com
Berger
Jacob
J
Clark
Robin D
RD
Sethofer
Steven G
SG
Krauss
Nancy E
NE
Brothers
Julie M
JM
Martin
Renee S
RS
Misner
Dinah L
DL
Schwab
Dietmar
D
Alexandrova
Ludmila
L
D000818:Animals; D008956:Models, Chemical; D010078:Oxazines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C522193:3,4-dihydro-2H-benzo(1,4)oxazine; D010078:Oxazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor