title: Adenosine kinase inhibitors: polar 7-substitutent of pyridopyrimidine derivatives improving their locomotor selectivity.
abstract: We have discovered that polar 7-substituents of pyridopyrimidine derivatives affect not only whole cell AK inhibitory potency, but also selectivity in causing locomotor side effects in vivo animal models. We have identified compound, 1o, which has potent whole cell AK inhibitory potency, analgesic activity and minimal reduction of locomotor activity.
authors.affiliation: Abbott Laboratories, Neuroscience Research, Bldg. AP9A LL, 100 Abbott Park Road, Abbott Park, IL 60064-6115, USA. guozhu.zheng@abbott.com
authors.forename: Guo Zhu
authors.initials: GZ
authors.lastname: Zheng
authors.forename: Yue
authors.initials: Y
authors.lastname: Mao
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: John K
authors.initials: JK
authors.lastname: Pratt
authors.forename: John R
authors.initials: JR
authors.lastname: Koenig
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Perner
authors.forename: Marlon D
authors.initials: MD
authors.lastname: Cowart
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Gfesser
authors.forename: Steve
authors.initials: S
authors.lastname: McGaraughty
authors.forename: Katharine L
authors.initials: KL
authors.lastname: Chu
authors.forename: Chang
authors.initials: C
authors.lastname: Zhu
authors.forename: Haixia
authors.initials: H
authors.lastname: Yu
authors.forename: Kathy
authors.initials: K
authors.lastname: Kohlhaas
authors.forename: Karen M
authors.initials: KM
authors.lastname: Alexander
authors.forename: Carol T
authors.initials: CT
authors.lastname: Wismer
authors.forename: Joseph
authors.initials: J
authors.lastname: Mikusa
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kowaluk
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Stewart
mesh_terms: D000248:Adenosine Kinase / Q000037:antagonists & inhibitors*; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D009043:Motor Activity / Q000187:drug effects*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D000248:Adenosine Kinase