A new series of antiallergic agents. II. Synthesis and activity of new 6,11-dihydrodibenz[b,e]oxepin-carboxylic acid derivatives.
New methods for the preparation of multi-functionalized-6,11-dihydrodibenz[b,e]oxepins were developed. The structural requirements of KW-4994 (1), a promising orally active antiallergic agent, were defined. A carboxyl group at C-2 was critical for enhanced antiallergic activity of 1. The introduction of bromine atom at C-9 of 1 could elongate the duration of the action of the parent. Antiplatelet activity, a new pharmacological property of this series of compounds, was observed in one of the derivatives of 1.
Kumazawa
T
T
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Ohshima
E
E
Harakawa
H
H
Sato
H
H
Obase
H
H
Oiji
Y
Y
Ishii
A
A
Ishii
H
H
Ohmori
K
K
D000818:Animals; D001584:Benzoxepins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D003342:Corpus Striatum / Q000378:metabolism; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D001584:Benzoxepins; D006634:Histamine H1 Antagonists; D011950:Receptors, Cholinergic