title: Pyridopyrimidine analogues as novel adenosine kinase inhibitors.
abstract: 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.
authors.affiliation: Abbott Laboratories, Dept. 4PM, Bldg. AP9A LL, 100 Abbott Park Road, Abbott Park, IL 60064-6115, USA. guozhu.zheng@abbott.com
authors.forename: G Z
authors.initials: GZ
authors.lastname: Zheng
authors.forename: C
authors.initials: C
authors.lastname: Lee
authors.forename: J K
authors.initials: JK
authors.lastname: Pratt
authors.forename: R J
authors.initials: RJ
authors.lastname: Perner
authors.forename: M Q
authors.initials: MQ
authors.lastname: Jiang
authors.forename: A
authors.initials: A
authors.lastname: Gomtsyan
authors.forename: M A
authors.initials: MA
authors.lastname: Matulenko
authors.forename: Y
authors.initials: Y
authors.lastname: Mao
authors.forename: J R
authors.initials: JR
authors.lastname: Koenig
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Muchmore
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.forename: K
authors.initials: K
authors.lastname: Kohlhaas
authors.forename: K M
authors.initials: KM
authors.lastname: Alexander
authors.forename: S
authors.initials: S
authors.lastname: McGaraughty
authors.forename: K L
authors.initials: KL
authors.lastname: Chu
authors.forename: C T
authors.initials: CT
authors.lastname: Wismer
authors.forename: J
authors.initials: J
authors.lastname: Mikusa
authors.forename: M F
authors.initials: MF
authors.lastname: Jarvis
authors.forename: K
authors.initials: K
authors.lastname: Marsh
authors.forename: E A
authors.initials: EA
authors.lastname: Kowaluk
authors.forename: S S
authors.initials: SS
authors.lastname: Bhagwat
authors.forename: A O
authors.initials: AO
authors.lastname: Stewart
mesh_terms: D000248:Adenosine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D009025:Morpholines; C115711:PD 173074; D011743:Pyrimidines; C416933:ABT 702; D000248:Adenosine Kinase