Ong H H, Caldwell S R, Profitt J A, Tegeler J J, Agnew M N, Wilker J C, Ress R J, Kitzen J M
Department of Chemical Research, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, New Jersey 08876.
J Med Chem. 1987 Dec;30(12):2295-303. doi: 10.1021/jm00395a020.
A series of [(6,7-dichlorobenzo[b]thien-5-yl)oxy]acetic acids and their corresponding 1,1-dioxides were synthesized and evaluated for diuretic activity in the acute saline loaded mice (ASLM) and hypotensive activity in the spontaneously hypertensive rat (SHR). A significant number of compounds were found to display potent activity in one or both assays, and preliminary structure-activity relationships with respect to each assay were delineated. Compound 94, the 1,1-dioxide of [(6,7-dichloro-2-n-propylbenzo[b]thien-5-yl)oxy]acetic acid was markedly active in both the ASLM and SHR by oral administration. The combined diuretic/hypotensive profile of this compound was further substantiated by its good saluretic response in water loaded conscious dogs and a moderate to good activity in renal hypertensive rats and sinoaortic-deafferented hypertensive dogs.
合成了一系列[(6,7 - 二氯苯并[b]噻吩 - 5 - 基)氧基]乙酸及其相应的1,1 - 二氧化物，并在急性盐水负荷小鼠（ASLM）中评估其利尿活性，在自发性高血压大鼠（SHR）中评估其降压活性。发现大量化合物在一种或两种试验中显示出强效活性，并描绘了每种试验的初步构效关系。化合物94，即[(6,7 - 二氯 - 2 - 正丙基苯并[b]噻吩 - 5 - 基)氧基]乙酸的1,1 - 二氧化物，经口服给药在ASLM和SHR中均具有显著活性。该化合物的联合利尿/降压特性在水负荷清醒犬的良好利钠反应以及肾性高血压大鼠和去窦主动脉神经高血压犬的中度至良好活性中得到进一步证实。
