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5-(3-Bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine: structure-activity relationships of 7-substituted heteroaryl analogs as non-nucleoside adenosine kinase inhibitors.

Abstract：

:4-Amino-5,7-disubstituted pyridopyrimidines are potent, non-nucleoside inhibitors of adenosine kinase (AK). We recently identified a potent, orally efficacious analog, 4 containing a 7-pyridylmorpholine substituted ring system as the key structural element of this template. In this report, we disclose the pharmacologic effects of five- and six-membered heterocyclic ring replacements for the pyridine ring in 4. These replacements were found to have interesting effects on in vivo efficacy and genotoxicity as well as in vitro potency. We discovered that the nitrogen in the heterocyclic ring at C(7) is important for the modulation of mutagenic side effects (Ames assay).

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Matulenko MA,Lee CH,Jiang M,Frey RR,Cowart MD,Bayburt EK,Didomenico S,Gfesser GA,Gomtsyan A,Zheng GZ,McKie JA,Stewart AO,Yu H,Kohlhaas KL,Alexander KM,McGaraughty S,Wismer CT,Mikusa J,Marsh KC,Snyder RD,Diehl MS,

doi

10.1016/j.bmc.2005.03.023

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

3705-20

issue

11

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(05)00232-4

journal_volume

13

pub_type

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