328527-11-3Relevant 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).
Pyridopyrimidine analogues as novel adenosine kinase inhibitors
Zheng, Guo Zhu,Lee, Chih-Hung,Pratt, John K.,Perner, Richard J.,Jiang, Mei Qun,Gomtsyan, Arthur,Matulenko, Mark A.,Mao, Yui,Koenig, John R.,Kim, Ki H.,Muchmore, Steve,Yu, Haixia,Kohlhaas, Kathy,Alexander, Karen M.,McGaraughty, Steve,Chu, Katharine L.,Wismer, Carol T.,Mikusa, Joseph,Jarvis, Michael F.,Marsh, Kennan,Kowaluk, Elizabeth A.,Bhagwat, Shripad S.,Stewart, Andrew O.
, p. 2071 - 2074 (2007/10/03)
A novel series of pyridopyrimidine analogues 9 was identified as potent adenosine kinase inhibitors based on the SAR and computational studies. Substitution of the C7 position of the pyridopyrimidino core with C2′ substituted pyridino moiety increased the in vivo potency and enhanced oral bioavailability of these adenosine kinase inhibitors.
