Inhibition of adenosine deaminase by analogues of adenosine and inosine, incorporating a common heterocyclic base, 4(7)-amino-6(5)H-imidazo[4,5-d]pyridazin-7(4)one

被引：8

作者：

Ujjinamatada, Ravi K. ^{[1
]}

Phatak, Pornima ^{[2
]}

Burger, Angelika M. ^{[2
]}

Hosmane, Ramachandra S. ^{[1
]}

机构：

[1] Univ Maryland, Dept Chem & Biochem, Lab Drug Design & Synth, Baltimore, MD 21250 USA

[2] Univ Maryland, Sch Med, Expt Therapeut Program, Marlene & Stewart Greenbaum Canc Ctr, Baltimore, MD 21201 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 03期

关键词：

D O I：

10.1021/jm700931t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Four nucleoside analogues (1-4) containing a common heterocyclic base, 4(7)-ammo-6(5)H-imidazo[4,5-d]pyridazin-7(4)one, were screened against calf-intestine adenosine deaminase. Compounds I and 3 with K-i values of 10-12 mu M are more than four times as potent inhibitors of ADA compared with 2 and 4, with K-i values of 51-52 mu M. Also, 3 is not a substrate of ADA. Nucleosides 3 and 4 also exhibit moderate in vitro activity against breast cancer cell lines, while all four are only minimally or nontoxic to the normal cells.

引用

页码：694 / 698

页数：5

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