Levenson C H, Meyer R B
J Med Chem. 1984 Feb;27(2):228-32. doi: 10.1021/jm00368a022.
Three new heterocyclic analogues (4-6) of dihydroorotic acid were designed, synthesized, and tested as inhibitors of dihydroorotase. Each compound possessed a tetrahedral sulfur atom at the position equivalent to carbon 4 in the dihydroorotate ring in an attempt to mimic the presumed tetrahedral transition state in the course of the enzymatic reaction. Additionally, N-carbamyl-3-phosphonoalanine was prepared and evaluated as a dihydroorotase inhibitor. Compounds 4 and 6 were modest inhibitors (I50's of 0.52 and 0.18 mM, respectively), but the other candidate inhibitors showed little inhibition at 1 mM.
设计、合成了三种新型二氢乳清酸杂环类似物（4-6），并将其作为二氢乳清酸酶抑制剂进行测试。每种化合物在与二氢乳清酸环中4位碳原子等效的位置上都有一个四面体硫原子，试图模拟酶促反应过程中假定的四面体过渡态。此外，制备了N-氨甲酰基-3-膦酰基丙氨酸并将其作为二氢乳清酸酶抑制剂进行评估。化合物4和6是适度的抑制剂（I50分别为0.52和0.18 mM），但其他候选抑制剂在1 mM时几乎没有抑制作用。
