Synthesis and biological activity of 11-[4-(cinnamyl)-1-piperazinyl]- 6,11-dihydrodibenz[b,e]oxepin derivatives, potential agents for the treatment of cerebrovascular disorders.
A series of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e] oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3- phenyl-2-propenyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities. Compound 50 also shows an inhibitory effect against cerebral edema as well when orally given to rats.
Kurokawa
M
M
Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Sato
F
F
Masuda
Y
Y
Yoshida
T
T
Ochi
Y
Y
Zushi
K
K
Fujiwara
I
I
Naruto
S
S
Uno
H
H
Matsumoto
J
J
D000818:Animals; D001582:Benzothiepins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001584:Benzoxepins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001929:Brain Edema / Q000188:drug therapy; D002545:Brain Ischemia / Q000188:drug therapy; D002561:Cerebrovascular Disorders / Q000188:drug therapy*; D005444:Flunarizine / Q000494:pharmacology / Q000627:therapeutic use; D002534:Hypoxia, Brain / Q000188:drug therapy; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship
D001582:Benzothiepins; D001584:Benzoxepins; D010879:Piperazines; D005444:Flunarizine