Study on Inhibitors of Methionine Synthase Ⅷ:Synthesis of 2,5-Diamino-4-oxo-6- （3-butenyl） pyrimidine
作者单位：Department of Chemistry University of Newcastle Newcastle upon Tyne England Department of Chemistry University of Newcastle Newcastle upon Tyne England
会议名称：《第三届全国有机化学学术会议》
会议日期：2004年
学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学]
基 金：Project supported by the National Natural Science Foundation of China (20172007)
摘 要：正 Cobalamin-dependent methionine synthase plays a crucial role in folate metabolism and such would appear to be an excellent target for rational antifolate drug design. However, to date, no anticancer agents directed at this enzyme are available, but the enzyme is efficiently and specifically inhibited by N2O and this has proven invaluable for evaluating the biochemical consequence of enzyme inhibition and for mechanistic studies.2,5-Diamino-4-oxo-6-（3-butenyl）pyrimidine, a key intermediate in synthetic inhibitors of methionine synthase, was first synthesized using γ-butenyl-β-ketoester and guanidine carbonate （Scheme 1）.