title: Synthesis and biological evaluation of pteridine and pyrazolopyrimidine based adenosine kinase inhibitors.
abstract: Three new approaches have been tested to modify existing pyridopyrimidine and alkynylpyrimidine classes of nonnucleoside adenosine kinase inhibitors 2 and 3. 4-Amino-substituted pteridines 8a-e were generally less active than corresponding 5- and 6-substituted pyridopyrimidines 2. Pyrazolopyrimidine 13c with IC(50)=7.5 nM was superior to its open chain alkynylpyrimidine analog 13g (IC(50)=22 nM) while pyrrolopyrimidines such as 17a were inactive.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. arthur.r.gomtsyan@abbott.com
authors.forename: Arthur
authors.initials: A
authors.lastname: Gomtsyan
authors.forename: Stanley
authors.initials: S
authors.lastname: Didomenico
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Stewart
authors.forename: Shripad S
authors.initials: SS
authors.lastname: Bhagwat
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kowaluk
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
mesh_terms: D000248:Adenosine Kinase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011621:Pteridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011621:Pteridines; D011720:Pyrazoles; D011743:Pyrimidines; D000248:Adenosine Kinase