Adenosine kinase inhibitors: polar 7-substitutent of pyridopyrimidine derivatives improving their locomotor selectivity

Guo Zhu Zheng; Yue Mao; Chih-Hung Lee; John K Pratt; John R Koenig; Richard J Perner; Marlon D Cowart; Gregory A Gfesser; Steve McGaraughty; Katharine L Chu; Chang Zhu; Haixia Yu; Kathy Kohlhaas; Karen M Alexander; Carol T Wismer; Joseph Mikusa; Michael F Jarvis; Elizabeth A Kowaluk; Andrew O Stewart

doi:10.1016/s0960-894x(03)00642-5

Adenosine kinase inhibitors: polar 7-substitutent of pyridopyrimidine derivatives improving their locomotor selectivity

Bioorg Med Chem Lett. 2003 Sep 15;13(18):3041-4. doi: 10.1016/s0960-894x(03)00642-5.

Affiliation

¹ Abbott Laboratories, Neuroscience Research, Bldg. AP9A LL, 100 Abbott Park Road, Abbott Park, IL 60064-6115, USA. [email protected]

PMID: 12941329
DOI: 10.1016/s0960-894x(03)00642-5

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.

MeSH terms

Adenosine Kinase / antagonists & inhibitors*
Analgesics / chemical synthesis*
Analgesics / pharmacology
Animals
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Hyperalgesia / drug therapy
Inhibitory Concentration 50
Motor Activity / drug effects*
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology
Structure-Activity Relationship

Substances

Analgesics
Enzyme Inhibitors
Pyrimidines
Adenosine Kinase