Nakai H, Konno M, Kosuge S, Sakuyama S, Toda M, Arai Y, Obata T, Katsube N, Miyamoto T, Okegawa T
Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
J Med Chem. 1988 Jan;31(1):84-91. doi: 10.1021/jm00396a013.
(p-Amylcinnamoyl)anthranilic acid (3a) had moderate antagonist activities against LTD4-induced smooth muscle contraction on guinea pig ileum and LTC4-induced bronchoconstriction in anesthetized guinea pigs. Modifications were made in the hydrophobic part (cinnamoyl moiety) and the hydrophilic part (anthranilate moiety) of 3a. A series of 8-(benzoylamino)-2-tetrazol-5-yl-1,4-benzodioxans and 8-(benzoylamino)-2-tetrazol-5-yl-4-oxo-4H-1-benzopyrans were revealed to be potent antagonists of leukotrienes C4 and D4. Among both series, ONO-RS-347 (18k) and ONO-RS-411 (19h) were the most potent and orally active antagonists, respectively. Structure-activity relationships are discussed.
（对戊基肉桂酰基）邻氨基苯甲酸（3a）对LTD4诱导的豚鼠回肠平滑肌收缩和LTC4诱导的麻醉豚鼠支气管收缩具有中等程度的拮抗活性。对3a的疏水部分（肉桂酰基部分）和亲水部分（邻氨基苯甲酸盐部分）进行了修饰。一系列8-（苯甲酰氨基）-2-四唑-5-基-1,4-苯并二恶烷和8-（苯甲酰氨基）-2-四唑-5-基-4-氧代-4H-1-苯并吡喃被发现是白三烯C4和D4的强效拮抗剂。在这两个系列中，ONO-RS-347（18k）和ONO-RS-411（19h）分别是最有效的口服活性拮抗剂。讨论了构效关系。
