title: Discovery of aminoquinazoline derivatives as human A(2A) adenosine receptor antagonists.
abstract: Novel bicyclic adenosine A(2A) antagonists with an aminoquinazoline moiety were designed and synthesized. The optimization of the initial lead compound based on in vitro and in vivo activity has led to the discovery of a potent and selective class of adenosine A(2A) antagonists. The structure-activity relationships of this novel series of bicyclic aminoquinazoline derivatives as adenosine A(2A) antagonists are described in detail.
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Aslanian
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Gioconda
authors.initials: G
authors.lastname: Gallo
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Tanweer
authors.initials: T
authors.lastname: Khan
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Rongze
authors.initials: R
authors.lastname: Kuang
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Biju
authors.initials: B
authors.lastname: Purakkattle
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: De Ruiz
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stamford
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Pauline
authors.initials: P
authors.lastname: Ting
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Heping
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Hongwu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
authors.forename: Yonglian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Deborra
authors.initials: D
authors.lastname: Mullins
authors.affiliation: Department of Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Hodgson
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D006207:Half-Life; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D011799:Quinazolines; D043705:Receptor, Adenosine A2A
keywords: Adenosine A(2A) receptor antagonist; Aminoquinazoline; Parkinson’s disease