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Structure-activity studies of 5-substituted pyridopyrimidines as adenosine kinase inhibitors.

Abstract：

:The synthesis and SAR of a novel series of non-nucleoside pyridopyrimidine inhibitors of the enzyme adenosine kinase (AK) are described. It was found that pyridopyrimidines with a broad range of medium and large non-polar substituents at the 5-position potently inhibited AK activity. A narrower range of analogues was capable of potently inhibiting adenosine phosphorylation in intact cells indicating an enhanced ability of these analogues to penetrate cell membranes. Potent AK inhibitors were found to effectively reduce nociception in animal models of thermal hyperalgesia and persistent pain.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Cowart M,Lee CH,Gfesser GA,Bayburt EK,Bhagwat SS,Stewart AO,Yu H,Kohlhaas KL,McGaraughty S,Wismer CT,Mikusa J,Zhu C,Alexander KM,Jarvis MF,Kowaluk EA

doi

10.1016/s0960-894x(00)00602-8

subject

Has Abstract

pub_date

2001-01-08 00:00:00

pages

83-6

issue

1

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(00)00602-8

journal_volume

11

pub_type

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