214697-26-4Relevant articles and documents
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
Matulenko, Mark A.,Lee, Chih-Hung,Jiang, Meiqun,Frey, Robin R.,Cowart, Marlon D.,Bayburt, Erol K.,DiDomenico Jr., Stanley,Gfesser, Gregory A.,Gomtsyan, Arthur,Guo, Zhu Zheng,McKie, Jeffery A.,Stewart, Andrew O.,Yu, Haixia,Kohlhaas, Kathy L.,Alexander, Karen M.,McGaraughty, Steve,Wismer, Carol T.,Mikusa, Joseph,Marsh, Kennan C.,Snyder, Ronald D.,Diehl, Marilyn S.,Kowaluk, Elizabeth A.,Jarvis, Michael F.,Bhagwat, Shripad S.
, p. 3705 - 3720 (2007/10/03)
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).
Structure-activity studies of 5-substituted pyridopyrimidines as adenosine kinase inhibitors
Cowart, Marlon,Lee, Chih-Hung,Gfesser, Gregory A.,Bayburt, Erol K.,Bhagwat, Shripad S.,Stewart, Andrew O.,Yu, Haixia,Kohlhaas, Kathy L.,McGaraughty, Steve,Wismer, Carol T.,Mikusa, Joseph,Zhu, Chang,Alexander, Karen M.,Jarvis, Michael F.,Kowaluk, Elizabeth A.
, p. 83 - 86 (2007/10/03)
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. (C) 2000 Elsevier Science Ltd.