title: Design and synthesis of novel 3-(benzo[d]oxazol-2-yl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine derivatives as selective G-protein-coupled receptor kinase-2 and -5 inhibitors.
abstract: G-protein-coupled receptor kinase (GRK)-2 and -5 are emerging therapeutic targets for the treatment of cardiovascular disease. In our efforts to discover novel small molecules to inhibit GRK-2 and -5, a class of compound based on 3-(benzo[d]oxazol-2-yl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine was identified as a novel hit by high throughput screening campaign. Structural modification of parent benzoxazole scaffolds by introducing substituents on phenyl displayed potent inhibitory activities toward GRK-2 and -5.
authors.affiliation: Research Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-343, Republic of Korea.
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Cho
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Lee
authors.forename: Heejung
authors.initials: H
authors.lastname: Jung
authors.forename: Chang Soo
authors.initials: CS
authors.lastname: Yun
authors.forename: Jae Du
authors.initials: JD
authors.lastname: Ha
authors.forename: Hyoung Rae
authors.initials: HR
authors.lastname: Kim
authors.forename: Chong Hak
authors.initials: CH
authors.lastname: Chae
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Seo
authors.forename: Kwang-Seok
authors.initials: KS
authors.lastname: Oh
mesh_terms: D000588:Amines / Q000737:chemistry*; D001583:Benzoxazoles / Q000737:chemistry; D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062105:Molecular Docking Simulation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D001583:Benzoxazoles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; C031280:pyrazole; D054769:G-Protein-Coupled Receptor Kinase 2; D054774:G-Protein-Coupled Receptor Kinase 5; C023666:pyridine
keywords: Benzoxazole; G-protein-coupled receptor kinase-2 (GRK-2); GRK-5; Heart failure