Park J S, Chang C T, Mertes M P
J Med Chem. 1979 Sep;22(9):1134-7. doi: 10.1021/jm00195a027.
In a study of the sequence steps involved in the mechanism of thymidylate synthetase catalysis, 5-[(N-methyl-piperazinyl)methyl]- (5) and 5-[(4-methyl-1,2,3,4-tetrahydroquinoxalyl)methyl]-2'-deoxyuridine 5'-phosphate (6) were synthesized. Compound 6 has high affinity for the Lactobacillus casei enzyme (Ki = 0.75 microM, KI/Km - 0.23), which is 50 times stronger than that of the piperazinyl derivative 5. Compound 6, a possible multisubstrate inhibitor, is an analogue of a proposed intermediate in the reaction mechanism wherein the enzyme is eliminated from the covalent complex (enzyme--substrate--cofactor) prior to the redox reaction leading to the products 2'-deoxythymidine 5'-phosphate and 7,8-dihydrofolic acid.
在一项关于胸苷酸合成酶催化机制所涉及的序列步骤的研究中，合成了5-[(N-甲基-哌嗪基)甲基]-(5)和5-[(4-甲基-1,2,3,4-四氢喹喔啉基)甲基]-2'-脱氧尿苷5'-磷酸(6)。化合物6对干酪乳杆菌酶具有高亲和力（Ki = 0.75 microM，KI/Km - 0.23），比哌嗪基衍生物5的亲和力强50倍。化合物6是一种可能的多底物抑制剂，是反应机制中一种假定中间体的类似物，在该反应机制中，在导致产物2'-脱氧胸苷5'-磷酸和7,8-二氢叶酸的氧化还原反应之前，酶从共价复合物（酶-底物-辅因子）中被消除。
