title: Discovery and optimization of 2-aryl oxazolo-pyrimidines as adenosine kinase inhibitors using liquid phase parallel synthesis.
abstract: Adenosine kinase inhibition is an attractive therapeutic approach for several conditions for example, neurodegeneration, seizures, ischemia, inflammation and pain. Several nucleosidic and non-nucleosidic inhibitors are available. Using a virtual screening approach, we have discovered that 2-aryl oxazolo-pyrimidines are adenosine kinase inhibitors. Subsequent high throughput derivatization enabled the optimization of this new inhibitor chemotype resulting in highly potent derivatives. A variety of analogues were produced by applying liquid phase parallel synthesis to vary the 7-amino residues as well as the 2-aryl moiety.
authors.affiliation: BAYER AG, Bayer Health Care, Division Pharma, Medicinal Chemistry, Germany. marcus.bauser.mb@bayer-ag.de
authors.forename: M
authors.initials: M
authors.lastname: Bauser
authors.forename: G
authors.initials: G
authors.lastname: Delapierre
authors.forename: M
authors.initials: M
authors.lastname: Hauswald
authors.forename: T
authors.initials: T
authors.lastname: Flessner
authors.forename: D
authors.initials: D
authors.lastname: D'Urso
authors.forename: A
authors.initials: A
authors.lastname: Hermann
authors.forename: B
authors.initials: B
authors.lastname: Beyreuther
authors.forename: J
authors.initials: J
authors.lastname: De Vry
authors.forename: P
authors.initials: P
authors.lastname: Spreyer
authors.forename: E
authors.initials: E
authors.lastname: Reissmüller
authors.forename: H
authors.initials: H
authors.lastname: Meier
mesh_terms: D000248:Adenosine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010080:Oxazoles; D011743:Pyrimidines; D000248:Adenosine Kinase