Kawashima Y, Amanuma F, Sato M, Okuyama S, Nakashima Y, Sota K, Moriguchi I
J Med Chem. 1986 Nov;29(11):2284-90. doi: 10.1021/jm00161a026.
4,6-Disubstituted 2-(morpholinocarbonyl)furo[3,2-b]indole derivatives showed analgesic and antiinflammatory activities when assayed by the acetic acid writhing test in mice and the carrageenin edema test in rats. To understand how the substituents affect the biological activities, the quantitative structure-activity relationships (QSAR) of 38 compounds were analyzed using the adaptive least-squares method (ALS method). The resulting QSAR suggested that some chemical modifications of 4,6-disubstituted furo[3,2-b]indole derivatives would improve their biological activities. Thus, 15 additional compounds were synthesized to reinforce and confirm the correlation. Among these compounds, particularly 4-(2-ethylhexanoyl)-2-(morpholinocarbonyl)-6-(trifluoromethy l) furo[3,2-b]indole showed pronounced biological activities. This compound gave a pharmacological activity spectrum similar to that of tiaramide but exhibited much higher potency.
通过小鼠醋酸扭体试验和大鼠角叉菜胶水肿试验测定，4,6-二取代的2-(吗啉甲酰基)呋喃并[3,2-b]吲哚衍生物显示出镇痛和抗炎活性。为了解取代基如何影响生物活性，使用自适应最小二乘法（ALS法）分析了38种化合物的定量构效关系（QSAR）。所得的QSAR表明，对4,6-二取代呋喃并[3,2-b]吲哚衍生物进行一些化学修饰将提高其生物活性。因此，合成了另外15种化合物以加强和确认这种相关性。在这些化合物中，特别是4-(2-乙基己酰基)-2-(吗啉甲酰基)-6-(三氟甲基)呋喃并[3,2-b]吲哚显示出显著的生物活性。该化合物给出了与替拉米特相似的药理活性谱，但表现出更高的效力。
