8-氨基-6-氟-9-β-D-呋喃核糖基-9H-嘌呤的合成及生化特性

Synthesis and biochemical properties of 8-amino-6-fluoro-9-beta-D-ribofuranosyl-9H-purine.

作者信息

Secrist J A, Bennett L L, Allan P W, Rose L M, Chang C H, Montgomery J A

出版信息

J Med Chem. 1986 Oct;29(10):2069-74. doi: 10.1021/jm00160a046.

Abstract

The synthesis and characterization of 8-amino-6-fluoro-9-beta-D-ribofuranosyl-9H-purine (3a) are presented. This compound is a substrate for adenosine deaminase and adenosine kinase. In L1210 cells 3a is converted to 8-aminoinosine monophosphate (4b), apparently by the action of AMP deaminase on the monophosphate of 3a, as well as to the triphosphate derivative of 3a. Pentostatin was used to inhibit adenosine deaminase, and coformycin was used to inhibit AMP deaminase in experiments designed to delineate the metabolic fate of 3a. Pentostatin was without influence on the cytotoxicity of 3a, but coformycin potentiated the cytotoxicity. The potentiation was associated with an increased cellular concentration of phosphates of 3a and a decreased concentration of 4b.

摘要

本文介绍了8-氨基-6-氟-9-β-D-呋喃核糖基-9H-嘌呤（3a）的合成与表征。该化合物是腺苷脱氨酶和腺苷激酶的底物。在L1210细胞中，3a显然通过AMP脱氨酶对3a单磷酸酯的作用转化为8-氨基肌苷单磷酸（4b），以及3a的三磷酸衍生物。在旨在描绘3a代谢命运的实验中，喷司他丁用于抑制腺苷脱氨酶，助间型霉素用于抑制AMP脱氨酶。喷司他丁对3a的细胞毒性没有影响，但助间型霉素增强了细胞毒性。这种增强与3a磷酸盐的细胞浓度增加和4b浓度降低有关。