HISTIDINE DERIVATIVES AND METAL TRICARBONYL COMPLEXES THEREOF, PREPARATION METHOD THEREOF, AND CONTRAST MEDIUMS CONTAINING THE SAME

摘要

Histidine derivatives are provided to bind to the radioactive nuclei strongly and contain a functional group capable of easily binding to physiologically activating materials, so that the histidine derivatives and metal tricarbonyl complexes are useful as contrast mediums. Histidine derivatives represented by the formula(1) are provided, wherein R^1 is hydrogen, methyl group, ethyl group or tertiary butyl group; R^2 is hydrogen, t-butoxy carbonyl group, acetyl group, benzyl group or fluorenylmethoxycarbonyl group(Fmoc); L is at least one selected from the groups represented by the following structural formulae; Y is Cl, Br, I, N3, NH2, NCS, COOH or SH; n is an integer from 1 to 10 and m is 2; X is H or SO3H; and Z is NH2, NCS and SH. The preparation method of the histidine derivatives represented by the formula(1) comprises the steps of: protecting a carboxyl group and an amino group of histidine represented by the formula(3) with protecting groups to prepare the compound represented by the formula(4); and adding an alkylation reactant containing carboxyl group, amino group, sulfur hydrin group, hydroxy group or alkyl group into the compound represented by the formula(4), wherein the amino group-protecting group is selected from t-butoxycarbonyl amide group, ethoxycarbonyl amide group, benzyloxycarbonyl amide group, 9-fluorenylmethoxycarbonyl amide group, p-methoxycarbonyl amide group, p-methoxyphenyl group, diphenylmethyl group and diphenylmethylene group.