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Discovery of 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d]pyrimidine, an orally active, non-nucleoside adenosine kinase inhibitor..

Abstract：

:Adenosine (ADO) is an endogenous homeostatic inhibitory neuromodulator that reduces cellular excitability at sites of tissue injury and inflammation. Inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO, selectively increases ADO concentrations at sites of tissue trauma and enhances the analgesic and antiinflammatory actions of ADO. Optimization of the high-throughput screening lead, 4-amino-7-aryl-substituted pteridine (5) (AK IC(50) = 440 nM), led to the identification of compound 21 (4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido [2,3-d]pyrimidine, ABT-702), a novel, potent (AK IC(50) = 1.7 nM) non-nucleoside AK inhibitor with oral activity in animal models of pain and inflammation.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Lee CH,Jiang M,Cowart M,Gfesser G,Perner R,Kim KH,Gu YG,Williams M,Jarvis MF,Kowaluk EA,Stewart AO,Bhagwat SS

doi

10.1021/jm000314x

keywords:

subject

Has Abstract

pub_date

2001-06-21 00:00:00

pages

2133-8

issue

13

eissn

0022-2623

issn

1520-4804

pii

jm000314x

journal_volume

44

pub_type

杂志文章

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