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

作者：Cho Sung Yun; Lee Byung Ho; Jung Heejung; Yun Chang Soo; Du Ha Jae; Kim Hyoung Rae; Chae Chong Hak; Lee Jeong Hyun; Seo Ho Won; Oh Kwang Seok^*

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(24): 6711-6716.

DOI：10.1016/j.bmcl.2013.10.036

• Heart failure
• G-protein-coupled receptor kinase-2 (GRK-2)
• GRK-5
• Benzoxazole

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.

• 出版日期2013-12-15