title: Synthesis and biological evaluation of 6,7-disubstituted 4-aminopyrido[2,3-d]pyrimidines as adenosine kinase inhibitors.
abstract: The synthesis and structure-activity relationship of a series of 6,7-disubstituted 4-aminopyrido[2,3-d]pyrimidines as novel non-nucleoside adenosine kinase inhibitors is described. A variety of substituents, primarily aryl, at the C6 and C7 positions of the pyridopyrimidine core were found to yield analogues that are potent inhibitors of adenosine kinase. In contrast to the 5,7-disubstituted and 5,6,7-trisubstituted pyridopyrimidine series, these analogues exhibited only modest potency to inhibit AK in intact cells.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6115, USA. richard.j.perner@abbott.com
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Perner
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Meiqun
authors.initials: M
authors.lastname: Jiang
authors.forename: Yu-Gui
authors.initials: YG
authors.lastname: Gu
authors.forename: Stanley
authors.initials: S
authors.lastname: Didomenico
authors.forename: Erol K
authors.initials: EK
authors.lastname: Bayburt
authors.forename: Karen M
authors.initials: KM
authors.lastname: Alexander
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Kohlhaas
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Kowaluk
authors.forename: Shripad S
authors.initials: SS
authors.lastname: Bhagwat
mesh_terms: D000248:Adenosine Kinase / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D011743:Pyrimidines; D000248:Adenosine Kinase