非甾体抗炎药。2. 二苯并[b,e]氧杂䓬-3-乙酸的衍生物/类似物。

Nonsteroidal antiinflammatory agents. 2. Derivatives/analogues of dibenz[b,e]oxepin-3-acetic acid.

作者信息

Yoshioka Y, Kitagawa M, Oki M, Kubo S, Tagawa H, Ueno K, Tsukada W, Tsubokawa M, Kasahara A

出版信息

J Med Chem. 1978 Jul;21(7):633-9. doi: 10.1021/jm00205a008.

Abstract

6,11-Dhydro-11-oxodibenz[b,e]oxepins and some related compounds have been synthesized and evaluated for antiinflammatory effect according to the carrageenan paw edema method in rats. The structure-activity relationships have been discussed among acetic acid, carboxylic acid, alcohol, and tetrazole derivatives of dibenzoxepins and acetic acid derivatives of thienobenzoxepins and of the corresponding thiepins. The 3-isopropyl alcohol 9 and 11-deoxo-3-propionic acid (49) were more active than indomethacin but not as active as the title compound (i.e., 43). Carboxylic acids, tetrazoles, esters, amides, and ketones were less active than the corresponding acetic acids. Three compounds (31, 33, and 34) were evaluated for ulcerogenicity and lethality but none surpassed 6,11-dihydro-11-oxodibenz[b,e]oxepin-3-acetic acid (41) in therapeutic ratio.

摘要

已合成了6,11-二氢-11-氧代二苯并[b,e]氧杂䓬及其一些相关化合物，并根据角叉菜胶致大鼠足肿胀法对其抗炎作用进行了评估。讨论了二苯并氧杂䓬的乙酸、羧酸、醇和四唑衍生物以及噻吩并苯并氧杂䓬和相应硫杂䓬的乙酸衍生物之间的构效关系。3-异丙醇9和11-脱氧-3-丙酸（49）的活性比吲哚美辛高，但不如标题化合物（即43）。羧酸、四唑、酯、酰胺和酮的活性低于相应的乙酸。对三种化合物（31、33和34）进行了致溃疡和致死性评估，但在治疗指数方面，没有一种超过6,11-二氢-11-氧代二苯并[b,e]氧杂䓬-3-乙酸（41）。