Williams H W, Eichler E, Randall W C, Rooney C S, Cragoe E J, Streeter K B, Schwam H, Michelson S R, Patchett A A, Taub D
J Med Chem. 1983 Aug;26(8):1196-200. doi: 10.1021/jm00362a020.
Fourteen new 4-substituted 2,4-dioxobutanoic acids have been synthesized. These compounds, all of which contain lipophilic 4-substituents, are potent inhibitors in vitro of porcine liver glycolic acid oxidase. The I50 value of the two most potent representatives, 4-(4'-bromo[1,1'-biphenyl]-4-yl)-2, 4-dioxobutanoic acid (8) and 4-[4'-[[(3,4-dihydro-3-hydroxy-2H-1, 5-benzodioxepin-3-yl)methyl]thio][1,1'-biphenyl]-4-yl]-2, 4-dioxobutanoic acid (13) is 6 X 10(-8)M.
已合成了14种新的4-取代-2,4-二氧代丁酸。这些化合物均含有亲脂性的4-取代基，是猪肝脏乙醇酸氧化酶的强效体外抑制剂。两种活性最强的代表物，即4-(4'-溴[1,1'-联苯]-4-基)-2,4-二氧代丁酸(8)和4-[4'-[[(3,4-二氢-3-羟基-2H-1,5-苯并二氧杂卓-3-基)甲基]硫代][1,1'-联苯]-4-基]-2,4-二氧代丁酸(13)的半数抑制浓度（I50）值为6×10⁻⁸M。
