Yonetani Y, Iwaki K, Shinosaki T, Kawase-Hanafusa A, Harada H, van Es A A
Jpn J Pharmacol. 1987 Apr;43(4):389-98. doi: 10.1254/jjp.43.389.
5-Dimethylsulfamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxyli c acid (S-8666) was studied as a possible new uricosuric diuretic agent using rats and chimpanzees. Various new compounds belonging to the 5-sulfamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxylic acids were clearly diuretic with uricosuric activity in intraperitoneally oxonate-treated rats. S-8666 was chosen as a favorable candidate because its uricosuric activity due to the effects of tubular transport of uric acid were apparently more marked than those of known uricosuric agents such as probenecid, benzbromarone, tienilic acid and indacrinone in oxonate-treated rats. S-8666 was also uricosuric in rats not given urate oxidase inhibitor. The diuretic effect of S-8666 in oxonate-treated rats was as high-ceilinged as that of furosemide, while those of tienilic acid, indacrinone and a known compound of a 5-carbonyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxylic acid were rather low-ceilinged. These uricosuric and diuretic activities of S-8666 were manifested by two enantiomers, of which the (+)-enantiomer displayed predominantly uricosuric activity and the (-)-enantiomer, diuretic activity like furosemide. The new compound was also uricosuric and diuretic in chimpanzees, although the potency of the uricosuric activity was similar to that of probenecid and less than that of indacrinone. Thus, it seems that S-8666 is a different type of uricosuric diuretic from known agents which have already been tried in humans.
5 - 二甲基氨甲酰基 - 6,7 - 二氯 - 2,3 - 二氢苯并呋喃 - 2 - 羧酸（S - 8666）作为一种可能的新型促尿酸排泄利尿剂，在大鼠和黑猩猩身上进行了研究。在经腹腔注射氧嗪酸盐处理的大鼠中，各种属于5 - 氨甲酰基 - 6,7 - 二氯 - 2,3 - 二氢苯并呋喃 - 2 - 羧酸的新化合物均具有明显的利尿和促尿酸排泄活性。S - 8666被选为理想候选药物，因为在经氧嗪酸盐处理的大鼠中，其由于尿酸肾小管转运作用而产生的促尿酸排泄活性明显高于丙磺舒、苯溴马隆、替尼酸和茚达立酮等已知促尿酸排泄药物。在未给予尿酸氧化酶抑制剂的大鼠中，S - 8666也具有促尿酸排泄作用。S - 8666对经氧嗪酸盐处理的大鼠的利尿作用与呋塞米一样具有高效能，而替尼酸、茚达立酮以及一种已知的5 - 羰基 - 6,7 - 二氯 - 2,3 - 二氢苯并呋喃 - 2 - 羧酸化合物的利尿作用效能则相对较低。S - 8666的这些促尿酸排泄和利尿活性由两种对映体表现出来，其中（+） - 对映体主要表现出促尿酸排泄活性，而（ - ） - 对映体则表现出类似呋塞米的利尿活性。该新化合物在黑猩猩身上也具有促尿酸排泄和利尿作用，尽管其促尿酸排泄活性的效能与丙磺舒相似，且低于茚达立酮。因此，S - 8666似乎是一种与已在人体试验过的已知药物不同类型的促尿酸排泄利尿剂。
