SYNTHESIS AND ANTILEUKEMIC ACTIVITY OF CHYMOTRYPSIN-ACTIVATED DERIVATIVES OF 3'-AMINO-2',3'-DIDEOXYCYTIDINE - (SYNTHETIC NUCLEOSIDES AND NUCLEOTIDES .33.)

被引：0

作者：

KAWAGUCHI, T

SAKAIRI, H

KIMURA, S

YAMAGUCHI, T

SANEYOSHI, M

机构：

[1] HOKKAIDO UNIV, FAC PHARMACEUT SCI, SAPPORO, HOKKAIDO 060, JAPAN

[2] NISHI TOKYO UNIV, DEPT SCI BIOL, YAMANASHI 40901, JAPAN

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 1995年 / 43卷 / 03期

关键词：

3'-AMINO-2'; 3'-DIDEOXYCYTIDINE; PHENYLALANINE; CHYMOTRYPSIN; ENZYMATIC ACTIVATION; PRODRUG; P388;

D O I：

暂无

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

3'-Amino-2',3'-dideoxycytidine (8) was directly synthesized from 2'-deoxycytidine. 2',3'-Dideoxy-3'-(N-acyl-L-phenylalanylamino)cytidines (acyl = butoxycarbonyl (9a), acetyl (9b), benzoyl (9c), and n-hexanoyl (9d)) were synthesized as chymotrypsin-activated prodrugs of 8. This N-protection was required for activation by chymotrypsin to 8. In vitro, compound 8 showed high cytotoxic activity against P388 cells, but the prodrugs 9a-d were ineffective. In vivo, however, these prodrugs showed much higher activity than 8 in mice bearing P388 cells.

引用

页码：501 / 504

页数：4

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